U.S. patent application number 15/286486 was filed with the patent office on 2017-05-25 for biomarkers and methods for predicting preterm birth.
The applicant listed for this patent is Sera Prognostics, Inc.. Invention is credited to John Jay BONIFACE, Gregory Charles CRITCHFIELD, Tracey Cristine FLEISCHER, Durlin Edward HICKOK.
Application Number | 20170146548 15/286486 |
Document ID | / |
Family ID | 51538302 |
Filed Date | 2017-05-25 |
United States Patent
Application |
20170146548 |
Kind Code |
A1 |
HICKOK; Durlin Edward ; et
al. |
May 25, 2017 |
BIOMARKERS AND METHODS FOR PREDICTING PRETERM BIRTH
Abstract
The disclosure provides biomarker panels, methods and kits for
determining the probability for preterm birth in a pregnant female.
The present disclosure is based, in part, on the discovery that
certain proteins and peptides in biological samples obtained from a
pregnant female are differentially expressed in pregnant females
that have an increased risk of developing in the future or
presently suffering from preterm birth relative to matched
controls. The present disclosure is further based, in part, on the
unexepected discovery that panels combining one or more of these
proteins and peptides can be utilized in methods of determining the
probability for preterm birth in a pregnant female with relatively
high sensitivity and specificity. These proteins and peptides
dislosed herein serve as biomarkers for classifying test samples,
predicting a probability of preterm birth, monitoring of progress
of preterm birth in a pregnant female, either individually or in a
panel of biomarkers.
Inventors: |
HICKOK; Durlin Edward;
(Seattle, WA) ; BONIFACE; John Jay; (Salt Lake
City, UT) ; CRITCHFIELD; Gregory Charles; (Salt Lake
City, UT) ; FLEISCHER; Tracey Cristine; (Sandy,
UT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Sera Prognostics, Inc. |
Salt Lake City |
UT |
US |
|
|
Family ID: |
51538302 |
Appl. No.: |
15/286486 |
Filed: |
October 5, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14213861 |
Mar 14, 2014 |
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15286486 |
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61919586 |
Dec 20, 2013 |
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61798504 |
Mar 15, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 2800/368 20130101;
G01N 33/689 20130101; G01N 2800/60 20130101 |
International
Class: |
G01N 33/68 20060101
G01N033/68 |
Claims
1-6. (canceled)
7. A method of determining probability for preterm birth in a
pregnant female, the method comprising detecting a measurable
feature of each of N biomarkers selected from the biomarkers listed
in Tables 1 through 63 in a biological sample obtained from said
pregnant female, and analyzing said measurable feature to determine
the probability for preterm birth in said pregnant female.
8. The method of claim 7, wherein said measurable feature comprises
fragments or derivatives of each of said N biomarkers selected from
the biomarkers listed in Tables 1 through 63.
9. The method of claim 7, wherein said detecting a measurable
feature comprises quantifying an amount of each of N biomarkers
selected from the biomarkers listed in Tables 1 through 63,
combinations or portions and/or derivatives thereof in a biological
sample obtained from said pregnant female.
10. The method of claim 9, further comprising calculating the
probability for preterm birth in said pregnant female based on said
quantified amount of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63.
11. The method of claim 7, further comprising an initial step of
providing a biomarker panel comprising N of the biomarkers listed
in Tables 1 through 63.
12. The method of claim 7, further comprising an initial step of
providing a biological sample from the pregnant female.
13. The method of claim 7, further comprising communicating said
probability to a health care provider.
14. The method of claim 13, wherein said communication informs a
subsequent treatment decision for said pregnant female.
15. The method of claim 7, wherein N is a number selected from the
group consisting of 2 to 24.
16. The method of claim 15, wherein said N biomarkers comprise at
least two of the isolated biomarkers selected from the group
consisting of AFTECCVVASQLR, ELLESYIDGR, ITLPDFTGDLR, the
biomarkers set forth in Table 50, and the biomarkers set forth in
Table 52.
17-23. (canceled)
24. The method of claim 7, wherein said quantifying comprises mass
spectrometry (MS).
25. The method of claim 24, wherein said MS comprises liquid
chromatography-mass spectrometry (LC-MS).
26. The method of claim 24, wherein said MS comprises multiple
reaction monitoring (MRM) or selected reaction monitoring
(SRM).
27. The method of claim 26, wherein said MRM (or SRM) comprises
scheduled MRM (SRM).
28. The method of claim 7, wherein said quantifying comprises an
assay that utilizes a capture agent.
29-65. (canceled)
66. A method of prediciting GAB, the method comprising: (a)
quantifying in a biological sample obtained from said pregnant
female an amount of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63; (b) multiplying and/or
thresholding said amount by a predetermined coefficient, (c)
determining the predicted GAB birth in said pregnant female
comprising adding said individual products to obtain a total risk
score that corresponds to said predicted GAB.
67. A method of prediciting time to birth in a pregnant female, the
method comprising: (a) obtaining a biological sample from said
pregnant female; (b) quantifying an amount of each of N biomarkers
selected from the biomarkers listed in Tables 1 through 63 in said
biological sample; (c) multiplying and/or thresholding said amount
by a predetermined coefficient, (d) determining predicted GAB in
said pregnant female comprising adding said individual products to
obtain a total risk score that corresponds to said predicted GAB;
and (e) substracting the estimated GA at time biological sample was
obtained from the predicted GAB to predict time to birth in said
pregnant female.
68-79. (canceled)
Description
[0001] This application is a continuation of application Ser. No.
14/213,861, filed Mar. 14, 2014, which claims the benefit of U.S.
provisional patent application No. 61/919,586, filed Dec. 20, 2013,
and U.S. provisional application No. 61/798,504, filed Mar. 15,
2013, each of which is incorporated herein by reference in its
entirety.
[0002] This application incorporates by reference a Sequence
Listing submitted herewith as an ASCII text file entitled
13271-021-999_SL.txt created on Oct. 5, 2016, and having a size of
216,321 bytes.
[0003] The invention relates generally to the field of personalized
medicine and, more specifically to compositions and methods for
determining the probability for preterm birth in a pregnant
female.
BACKGROUND
[0004] According to the World Heath Organization, an estimated 15
million babies are born preterm (before 37 completed weeks of
gestation) every year. In almost all countries with reliable data,
preterm birth rates are increasing. See, World Health Organization;
March of Dimes; The Partnership for Maternal, Newborn & Child
Health; Save the Children, Born too soon: the global action report
on preterm birth, ISBN 9789241503433(2012). An estimated 1 million
babies die annually from preterm birth complications. Globally,
preterm birth is the leading cause of newborn deaths (babies in the
first four weeks of life) and the second leading cause of death
after pneumonia in children under five years. Many survivors face a
lifetime of disability, including learning disabilities and visual
and hearing problems.
[0005] Across 184 countries with reliable data, the rate of preterm
birth ranges from 5% to 18% of babies born. Blencowe et al.,
"National, regional and worldwide estimates of preterm birth." The
Lancet, 9; 379(9832):2162-72 (2012). While over 60% of preterm
births occur in Africa and south Asia, preterm birth is
nevertheless a global problem. Countries with the highest numbers
include Brazil, India, Nigeria and the United States of America. Of
the 11 countries with preterm birth rates over 15%, all but two are
in sub-Saharan Africa. In the poorest countries, on average, 12% of
babies are born too soon compared with 9% in higher-income
countries. Within countries, poorer families are at higher risk.
More than three-quarters of premature babies can be saved with
feasible, cost-effective care, for example, antenatal steroid
injections given to pregnant women at risk of preterm labour to
strengthen the babies' lungs.
[0006] Infants born preterm are at greater risk than infants born
at term for mortality and a variety of health and developmental
problems. Complications include acute respiratory,
gastrointestinal, immunologic, central nervous system, hearing, and
vision problems, as well as longer-term motor, cognitive, visual,
hearing, behavioral, social-emotional, health, and growth problems.
The birth of a preterm infant can also bring considerable emotional
and economic costs to families and have implications for
public-sector services, such as health insurance, educational, and
other social support systems. The greatest risk of mortality and
morbidity is for those infants born at the earliest gestational
ages. However, those infants born nearer to term represent the
greatest number of infants born preterm and also experience more
complications than infants born at term.
[0007] To prevent preterm birth in women who are less than 24 weeks
pregnant with an ultrasound showing cervical opening, a surgical
procedure known as cervical cerclage can be employed in which the
cervix is stitched closed with strong sutures. For women less than
34 weeks pregnant and in active preterm labor, hospitalization may
be necessary as well as the administration of medications to
temporarily halt preterm labor an/or promote the fetal lung
development. If a pregnant women is determined to be at risk for
preterm birth, health care providers can implement various clinical
strategies that may include preventive medications, for example,
hydroxyprogesterone caproate (Makena) injections and/or vaginal
progesterone gel, cervical pessaries, restrictions on sexual
activity and/or other physical activities, and alterations of
treatments for chronic conditions, such as diabetes and high blood
pressure, that increase the risk of preterm labor.
[0008] There is a great need to identify and provide women at risk
for preterm birth with proper antenatal care. Women identified as
high-risk can be scheduled for more intensive antenatal
surveillance and prophylactic interventions. Current strategies for
risk assessment are based on the obstetric and medical history and
clinical examination, but these strategies are only able to
identify a small percentage of women who are at risk for preterm
delivery. Reliable early identification of risk for preterm birth
would enable planning appropriate monitoring and clinical
management to prevent preterm delivery. Such monitoring and
management might include: more frequent prenatal care visits,
serial cervical length measurements, enhanced education regarding
signs and symptoms of early preterm labor, lifestyle interventions
for modifiable risk behaviors, cervical pessaries and progesterone
treatment. Finally, reliable antenatal identification of risk for
preterm birth also is crucial to cost-effective allocation of
monitoring resources.
[0009] The present invention addresses this need by providing
compositions and methods for determining whether a pregnant woman
is at risk for preterm birth. Related advantages are provided as
well.
SUMMARY
[0010] The present invention provides compositions and methods for
predicting the probability of preterm birth in a pregnant
female.
[0011] In one aspect, the invention provides a panel of isolated
biomarkers comprising N of the biomarkers listed in Tables 1
through 63. In some embodiments, N is a number selected from the
group consisting of 2 to 24. In additional embodiments, the
biomarker panel comprises at least two of the isolated biomarkers
selected from the group consisting of AFTECCVVASQLR, ELLESYIDGR,
and ITLPDFTGDLR. In additional embodiments, the biomarker panel
comprises at least two of the isolated biomarkers selected from the
group consisting of FLNWIK, FGFGGSTDSGPIR, LLELTGPK, VEHSDLSFSK,
IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER, DVLLLVHNLPQNLPGYFWYK,
SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK, and LSETNR
[0012] In further embodiments, the biomarker panel comprises at
least two of the isolated biomarkers selected from the group
consisting of the biomarkers set forth in Table 50 and the
biomarkers set forth in Table 52.
[0013] In a further aspect, the invention provides a panel of
isolated biomarkers comprising N of the biomarkers listed in Tables
1 through 63. In some embodiments, N is a number selected from the
group consisting of 2 to 24. In additional embodiments, the
biomarker panel comprises at least two of the isolated biomarkers
selected from the group consisting of the biomarkers set forth in
Table 50 and the biomarkers set forth in Table 52.
[0014] In some embodiments, the invention provides a biomarker
panel comprising at least two of the isolated biomarkers selected
from the group consisting of lipopolysaccharide-binding protein
(LBP), prothrombin (THRB), complement component C5 (C5 or CO5),
plasminogen (PLMN), and complement component C8 gamma chain (C8G or
CO8G).
[0015] In some embodiments, the invention provides a biomarker
panel comprising at least two of the isolated biomarkers selected
from the group consisting of Alpha-1B-glycoprotein (A1BG),
Disintegrin and metalloproteinase domain-containing protein 12
(ADA12), Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0016] In other embodiments, the invention provides a biomarker
panel comprising lipopolysaccharide-binding protein (LBP),
prothrombin (THRB), complement component C5 (C5 or CO5),
plasminogen (PLMN), complement component C8 gamma chain (C8G or
CO8G), complement component 1, q subcomponent, B chain (C1QB),
fibrinogen beta chain (FIBB or FIB), C-reactive protein (CRP),
inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), chorionic
somatomammotropin hormone (CSH), and angiotensinogen (ANG or
ANGT).
[0017] In other embodiments, the invention provides a biomarker
panel comprising Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0018] In additional embodiments, the invention provides a
biomarker panel comprising at least two of the isolated biomarkers
selected from the group consisting of the biomarkers set forth in
Table 51 and the biomarkers set forth in Table 53.
[0019] Also provided by the invention is a method of determining
probability for preterm birth in a pregnant female comprising
detecting a measurable feature of each of N biomarkers selected
from the biomarkers listed in Tables 1 through 63 in a biological
sample obtained from the pregnant female, and analyzing the
measurable feature to determine the probability for preterm birth
in the pregnant female. In some embodiments, the invention provides
a method of predicting GAB, the method encompassing detecting a
measurable feature of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63 in a biological sample
obtained from a pregnant female, and analyzing said measurable
feature to predict GAB.
[0020] In some embodiments, a measurable feature comprises
fragments or derivatives of each of the N biomarkers selected from
the biomarkers listed in Tables 1 through 63. In some embodiments
of the disclosed methods detecting a measurable feature comprises
quantifying an amount of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63, combinations or portions
and/or derivatives thereof in a biological sample obtained from the
pregnant female. In additional embodiments, the disclosed methods
of determining probability for preterm birth in a pregnant female
further encompass detecting a measurable feature for one or more
risk indicia associated with preterm birth.
[0021] In some embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of N biomarkers, wherein N is selected from the group
consisting of 2 to 24. In further embodiments, the disclosed
methods of determining probability for preterm birth in a pregnant
female and related methods disclosed herein comprise detecting a
measurable feature of each of at least two isolated biomarkers
selected from the group consisting of AFTECCVVASQLR, ELLESYIDGR,
and ITLPDFTGDLR. In further embodiments, the disclosed methods of
determining probability for preterm birth in a pregnant female and
related methods disclosed herein comprise detecting a measurable
feature of each of at least two isolated biomarkers selected from
the group consisting of FLNWIK, FGFGGSTDSGPIR, LLELTGPK,
VEHSDLSFSK, IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER,
DVLLLVHNLPQNLPGYFWYK, SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK,
and LSETNR. In further embodiments, the disclosed methods of
determining probability for preterm birth in a pregnant female and
related methods disclosed herein comprise detecting a measurable
feature of each of at least two isolated biomarkers selected from
the group consisting of the biomarkers set forth in Table 50 and
the biomarkers set forth in Table 52.
[0022] In other embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female comprise
detecting a measurable feature of each of at least two isolated
biomarkers selected from the group consisting of
lipopolysaccharide-binding protein (LBP), prothrombin (THRB),
complement component C5 (C5 or CO5), plasminogen (PLMN), and
complement component C8 gamma chain (C8G or CO8G).
[0023] In other embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female comprise
detecting a measurable feature of each of at least two isolated
biomarkers selected from the group consisting of
Alpha-1B-glycoprotein (A1BG), Disintegrin and metalloproteinase
domain-containing protein 12 (ADA12), Apolipoprotein B-100 (APOB),
Beta-2-microglobulin (B2MG), CCAAT/enhancer-binding protein
alpha/beta (HP8 Peptide), Corticosteroid-binding globulin (CBG),
Complement component C6, Endoglin (EGLN), Ectonucleotide
pyrophosphatase/phosphodiesterase family member 2 (ENPP2),
Coagulation factor VII (FA7), Hyaluronan-binding protein 2 (HABP2),
Pregnancy-specific beta-1-glycoprotein 9 (PSG9), Inhibin beta E
chain (INHBE).
[0024] In further embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female comprise
detecting a measurable feature of each of at least two isolated
biomarkers selected from the group consisting of
lipopolysaccharide-binding protein (LBP), prothrombin (THRB),
complement component C5 (C5 or CO5), plasminogen (PLMN), complement
component C8 gamma chain (C8G or CO8G), complement component 1, q
subcomponent, B chain (C1QB), fibrinogen beta chain (FIBB or FIB),
C-reactive protein (CRP), inter-alpha-trypsin inhibitor heavy chain
H4 (ITIH4), chorionic somatomammotropin hormone (CSH), and
angiotensinogen (ANG or ANGT).
[0025] In further embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female comprise
detecting a measurable feature of each of at least two isolated
biomarkers selected from the group consisting of the biomarkers set
forth in Table 51 and the biomarkers set forth in Table 53.
[0026] In some embodiments of the methods of determining
probability for preterm birth in a pregnant female, the probability
for preterm birth in the pregnant female is calculated based on the
quantified amount of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63. In some embodiments, the
disclosed methods for determining the probability of preterm birth
encompass detecting and/or quantifying one or more biomarkers using
mass sprectrometry, a capture agent or a combination thereof.
[0027] In some embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass an
initial step of providing a biomarker panel comprising N of the
biomarkers listed in Tables 1 through 63. In additional
embodiments, the disclosed methods of determining probability for
preterm birth in a pregnant female encompass an initial step of
providing a biological sample from the pregnant female.
[0028] In some embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass
communicating the probability to a health care provider. In
additional embodiments, the communication informs a subsequent
treatment decision for the pregnant female. In further embodiments,
the treatment decision of one or more selected from the group of
consisting of more frequent prenatal care visits, serial cervical
length measurements, enhanced education regarding signs and
symptoms of early preterm labor, lifestyle interventions for
modifiable risk behaviors and progesterone treatment.
[0029] In further embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass
analyzing the measurable feature of one or more isolated biomarkers
using a predictive model. In some embodiments of the disclosed
methods, a measurable feature of one or more isolated biomarkers is
compared with a reference feature.
[0030] In additional embodiments, the disclosed methods of
determining probability for preterm birth in a pregnant female
encompass using one or more analyses selected from a linear
discriminant analysis model, a support vector machine
classification algorithm, a recursive feature elimination model, a
prediction analysis of microarray model, a logistic regression
model, a CART algorithm, a flex tree algorithm, a LART algorithm, a
random forest algorithm, a MART algorithm, a machine learning
algorithm, a penalized regression method, and a combination
thereof. In one embodiment, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass
logistic regression.
[0031] In some embodiments, the invention provides a method of
determining probability for preterm birth in a pregnant female, the
method encompassing quantifying in a biological sample obtained
from the pregnant female an amount of each of N biomarkers selected
from the biomarkers listed in Tables 1 through 63; multiplying the
amount by a predetermined coefficient, and determining the
probability for preterm birth in the pregnant female comprising
adding the individual products to obtain a total risk score that
corresponds to the probability
[0032] In additional embodiments, the invention provides a method
of prediciting GAB, the method comprising: (a) quantifying in a
biological sample obtained from said pregnant female an amount of
each of N biomarkers selected from the biomarkers listed in Tables
1 through 63; (b) multiplying or thresholding said amount by a
predetermined coefficient, (c) determining the predicted GAB birth
in said pregnant female comprising adding said individual products
to obtain a total risk score that corresponds to said predicted
GAB.
[0033] In further embodiments, the invention provides a method of
prediciting time to birth in a pregnant female, the method
comprising: (a) obtaining a biological sample from said pregnant
female; (b) quantifying an amount of each of N biomarkers selected
from the biomarkers listed in Tables 1 through 63 in said
biological sample; (c) multiplying or thresholding said amount by a
predetermined coefficient, (d) determining predicted GAB in said
pregnant female comprising adding said individual products to
obtain a total risk score that corresponds to said predicted GAB;
and (e) substracting the estimated gestational age (GA) at time
biological sample was obtained from the predicted GAB to predict
time to birth in said pregnant female.
[0034] Other features and advantages of the invention will be
apparent from the detailed description, and from the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] FIG. 1. Scatterplot of actual gestational age at birth
versus predicted gestational age from random forest regression
model.
[0036] FIG 2. Distribution of predicted gestational age from random
forest regression model versus actual gestational age at birth
(GAB), where actual GAB is given in categories of (i) less than 37
weeks, (ii) 37 to 39 weeks, and (iii) 40 weeks or greater (peaks
left to right, respectively).
DETAILED DESCRIPTION
[0037] The present disclosure is based, in part, on the discovery
that certain proteins and peptides in biological samples obtained
from a pregnant female are differentially expressed in pregnant
females that have an increased risk of preterm birth relative to
controls. The present disclosure is further based, in part, on the
unexpected discovery that panels combining one or more of these
proteins and peptides can be utilized in methods of determining the
probability for preterm birth in a pregnant female with high
sensitivity and specificity. These proteins and peptides disclosed
herein serve as biomarkers for classifying test samples, predicting
probability of preterm birth, predicting probability of term birth,
predicting gestational age at birth (GAB), predicting time to birth
and/or monitoring of progress of preventative therapy in a pregnant
female, either individually or in a panel of biomarkers.
[0038] The disclosure provides biomarker panels, methods and kits
for determining the probability for preterm birth in a pregnant
female. One major advantage of the present disclosure is that risk
of developing preterm birth can be assessed early during pregnancy
so that appropriate monitoring and clinical management to prevent
preterm delivery can be initiated in a timely fashion. The present
invention is of particular benefit to females lacking any risk
factors for preterm birth and who would not otherwise be identified
and treated.
[0039] By way of example, the present disclosure includes methods
for generating a result useful in determining probability for
preterm birth in a pregnant female by obtaining a dataset
associated with a sample, where the dataset at least includes
quantitative data about biomarkers and panels of biomarkers that
have been identified as predictive of preterm birth, and inputting
the dataset into an analytic process that uses the dataset to
generate a result useful in determining probability for preterm
birth in a pregnant female. As described further below, this
quantitative data can include amino acids, peptides, polypeptides,
proteins, nucleotides, nucleic acids, nucleosides, sugars, fatty
acids, steroids, metabolites, carbohydrates, lipids, hormones,
antibodies, regions of interest that serve as surrogates for
biological macromolecules and combinations thereof.
[0040] In addition to the specific biomarkers identified in this
disclosure, for example, by accession number in a public database,
sequence, or reference, the invention also contemplates use of
biomarker variants that are at least 90% or at least 95% or at
least 97% identical to the exemplified sequences and that are now
known or later discovered and that have utility for the methods of
the invention. These variants may represent polymorphisms, splice
variants, mutations, and the like. In this regard, the instant
specification discloses multiple art-known proteins in the context
of the invention and provides exemplary accession numbers
associated with one or more public databases as well as exemplary
references to published journal articles relating to these
art-known proteins. However, those skilled in the art appreciate
that additional accession numbers and journal articles can easily
be identified that can provide additional characteristics of the
disclosed biomarkers and that the exemplified references are in no
way limiting with regard to the disclosed biomarkers. As described
herein, various techniques and reagents find use in the methods of
the present invention. Suitable samples in the context of the
present invention include, for example, blood, plasma, serum,
amniotic fluid, vaginal secretions, saliva, and urine. In some
embodiments, the biological sample is selected from the group
consisting of whole blood, plasma, and serum. In a particular
embodiment, the biological sample is serum. As described herein,
biomarkers can be detected through a variety of assays and
techniques known in the art. As further described herein, such
assays include, without limitation, mass spectrometry (MS)-based
assays, antibody-based assays as well as assays that combine
aspects of the two.
[0041] Protein biomarkers associated with the probability for
preterm birth in a pregnant female include, but are not limited to,
one or more of the isolated biomarkers listed in Tables 1 through
63. In addition to the specific biomarkers, the disclosure further
includes biomarker variants that are about 90%, about 95%, or about
97% identical to the exemplified sequences. Variants, as used
herein, include polymorphisms, splice variants, mutations, and the
like.
[0042] Additional markers can be selected from one or more risk
indicia, including but not limited to, maternal characteristics,
medical history, past pregnancy history, and obstetrical history.
Such additional markers can include, for example, previous low
birth weight or preterm delivery, multiple 2nd trimester
spontaneous abortions, prior first trimester induced abortion,
familial and intergenerational factors, history of infertility,
nulliparity, placental abnormalities, cervical and uterine
anomalies, short cervical length measurements, gestational
bleeding, intrauterine growth restriction, in utero
diethylstilbestrol exposure, multiple gestations, infant sex, short
stature, low prepregnancy weight, low or high body mass index,
diabetes, hypertension, urogenital infections (i.e. urinary tract
infection), asthma, anxiety and depression, asthma, hypertension,
hypothyroidism. Demographic risk indicia for preterm birth can
include, for example, maternal age, race/ethnicity, single marital
status, low socioeconomic status, maternal age, employment-related
physical activity, occupational exposures and environment exposures
and stress. Further risk indicia can include, inadequate prenatal
care, cigarette smoking, use of marijuana and other illicit drugs,
cocaine use, alcohol consumption, caffeine intake, maternal weight
gain, dietary intake, sexual activity during late pregnancy and
leisure-time physical activities. (Preterm Birth: Causes,
Consequences, and Prevention, Institute of Medicine (US) Committee
on Understanding Premature Birth and Assuring Healthy Outcomes;
Behrman R E, Butler A S, editors. Washington (D.C.): National
Academies Press (US); 2007). Additional risk indicia useful for as
markers can be identified using learning algorithms known in the
art, such as linear discriminant analysis, support vector machine
classification, recursive feature elimination, prediction analysis
of microarray, logistic regression, CART, FlexTree, LART, random
forest, MART, and/or survival analysis regression, which are known
to those of skill in the art and are further described herein.
[0043] Provided herein are panels of isolated biomarkers comprising
N of the biomarkers selected from the group listed in Tables 1
through 63. In the disclosed panels of biomarkers N can be a number
selected from the group consisting of 2 to 24. In the disclosed
methods, the number of biomarkers that are detected and whose
levels are determined, can be 1, or more than 1, such as 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22,
23, 24, 25 or more. In certain embodiments, the number of
biomarkers that are detected, and whose levels are determined, can
be 1, or more than 1, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more.
The methods of this disclosure are useful for determining the
probability for preterm birth in a pregnant female.
[0044] While certain of the biomarkers listed in Tables 1 through
63 are useful alone for determining the probability for preterm
birth in a pregnant female, methods are also described herein for
the grouping of multiple subsets of the biomarkers that are each
useful as a panel of three or more biomarkers. In some embodiments,
the invention provides panels comprising N biomarkers, wherein N is
at least three biomarkers. In other embodiments, N is selected to
be any number from 3-23 biomarkers.
[0045] In yet other embodiments, N is selected to be any number
from 2-5, 2-10, 2-15, 2-20, or 2-23. In other embodiments, N is
selected to be any number from 3-5, 3-10, 3-15, 3-20, or 3-23. In
other embodiments, N is selected to be any number from 4-5, 4-10,
4-15, 4-20, or 4-23. In other embodiments, N is selected to be any
number from 5-10, 5-15, 5-20, or 5-23. In other embodiments, N is
selected to be any number from 6-10, 6-15, 6-20, or 6-23. In other
embodiments, N is selected to be any number from 7-10, 7-15, 7-20,
or 7-23. In other embodiments, N is selected to be any number from
8-10, 8-15, 8-20, or 8-23. In other embodiments, N is selected to
be any number from 9-10, 9-15, 9-20, or 9-23. In other embodiments,
N is selected to be any number from 10-15, 10-20, or 10-23. It will
be appreciated that N can be selected to encompass similar, but
higher order, ranges.
[0046] In certain embodiments, the panel of isolated biomarkers
comprises one or more, two or more, three or more, four or more, or
five isolated biomarkers comprising an amino acid sequence selected
from AFTECCVVASQLR, ELLESYIDGR, ITLPDFTGDLR, TDAPDLPEENQAR and
SFRPFVPR. In some embodiments, the panel of isolated biomarkers
comprises one or more, two or more, three or more, four or more, or
five isolated biomarkers comprising an amino acid sequence selected
from FLNWIK, FGFGGSTDSGPIR, LLELTGPK, VEHSDLSFSK, IEGNLIFDPNNYLPK,
ALVLELAK, TQILEWAAER, DVLLLVHNLPQNLPGYFWYK, SEPRPGVLLR, ITQDAQLK,
ALDLSLK, WWGGQPLWITATK, and LSETNR.
[0047] In some embodiments, the panel of isolated biomarkers
comprises one or more, two or more, or three of the isolated
biomarkers consisting of an amino acid sequence selected from
AFTECCVVASQLR, ELLESYIDGR, and ITLPDFTGDLR. In some embodiments,
the panel of isolated biomarkers comprises one or more, two or
more, or three of the isolated biomarkers consisting of an amino
acid sequence selected from FLNWIK, FGFGGSTDSGPIR, LLELTGPK,
VEHSDLSFSK, IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER,
DVLLLVHNLPQNLPGYFWYK, SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK,
and LSETNR.
[0048] In some embodiments, the panel of isolated biomarkers
comprises one or more, two or more, or three of the isolated
biomarkers consisting of an amino acid sequence selected from the
biomarkers set forth in Table 50 and the biomarkers set forth in
Table 52.
[0049] In some embodiments, the panel of isolated biomarkers
comprises one or more peptides comprising a fragment from
lipopolysaccharide-binding protein (LBP), Schumann et al., Science
249 (4975), 1429-1431 (1990) (UniProtKB/Swiss-Prot: P18428.3);
prothrombin (THRB), Walz et al., Proc. Natl. Acad. Sci. U.S.A. 74
(5), 1969-1972(1977) (NCBI Reference Sequence: NP_000497.1);
complement component C5 (C5 or CO5) Haviland, J. Immunol. 146 (1),
362-368 (1991) (GenBank: AAA51925.1); plasminogen (PLMN) Petersen
et al., J. Biol. Chem. 265 (11), 6104-6111(1990) (NCBI Reference
Sequences: NP_000292.1 NP_001161810.1); and complement component C8
gamma chain (C8G or CO8G), Haefliger et al., Mol. Immunol. 28
(1-2), 123-131 (1991) (NCBI Reference Sequence: NP_000597.2).
[0050] In some embodiments, the panel of isolated biomarkers
comprises one or more peptides comprising a fragment from cell
adhesion molecule with homology to complement component 1, q
subcomponent, B chain (C1QB), Reid, Biochem. J. 179 (2), 367-371
(1979) (NCBI Reference Sequence: NP_000482.3); fibrinogen beta
chain (FIBB or FIB); Watt et al., Biochemistry 18 (1), 68-76 (1979)
(NCBI Reference Sequences: NP_001171670.1 and NP_005132.2);
C-reactive protein (CRP), Oliveira et al., J. Biol. Chem. 254 (2),
489-502 (1979) (NCBI Reference Sequence: NP_000558.2);
inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) Kim et al.,
Mol. Biosyst. 7 (5), 1430-1440 (2011) (NCBI Reference Sequences:
NP_001159921.1 and NP_002209.2); chorionic somatomammotropin
hormone (CSH) Selby et al., J. Biol. Chem. 259 (21), 13131-13138
(1984) (NCBI Reference Sequence: NP_001308.1); and angiotensinogen
(ANG or ANGT) Underwood et al., Metabolism 60(8):1150-7 (2011)
(NCBI Reference Sequence: NP_000020.1).
[0051] In additional embodiments, the invention provides a panel of
isolated biomarkers comprising N of the biomarkers listed in Tables
1 through 63. In some embodiments, N is a number selected from the
group consisting of 2 to 24. In additional embodiments, the
biomarker panel comprises at least two of the isolated biomarkers
selected from the group consisting of AFTECCVVASQLR, ELLESYIDGR,
and ITLPDFTGDLR. In additional embodiments, the biomarker panel
comprises at least two of the isolated biomarkers selected from the
group consisting of AFTECCVVASQLR, ELLESYIDGR, ITLPDFTGDLR,
TDAPDLPEENQAR and SFRPFVPR. In additional embodiments, the
biomarker panel comprises at least two of the isolated biomarkers
selected from the group consisting of FLNWIK, FGFGGSTDSGPIR,
LLELTGPK, VEHSDLSFSK, IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER,
DVLLLVHNLPQNLPGYFWYK, SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK,
and LSETNR.
[0052] In additional embodiments, the biomarker panel comprises at
least two of the isolated biomarkers selected from the group
consisting of the biomarkers set forth in Table 50 and the
biomarkers set forth in Table 52.
[0053] In further embodiments, the biomarker panel comprises at
least two of the isolated biomarkers selected from the group
consisting of lipopolysaccharide-binding protein (LBP), prothrombin
(THRB), complement component C5 (C5 or CO5), plasminogen (PLMN),
and complement component C8 gamma chain (C8G or CO8G). In another
embodiment, the invention provides a biomarker panel comprising at
least three isolated biomarkers selected from the group consisting
of lipopolysaccharide-binding protein (LBP), prothrombin (THRB),
complement component C5 (C5 or CO5), plasminogen (PLMN), and
complement component C8 gamma chain (C8G or CO8G).
[0054] In further embodiments, the biomarker panel comprises at
least two of the isolated biomarkers selected from the group
consisting of Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0055] In some embodiments, the invention provides a biomarker
panel comprising lipopolysaccharide-binding protein (LBP),
prothrombin (THRB), complement component C5 (C5 or CO5),
plasminogen (PLMN), complement component C8 gamma chain (C8G or
CO8G), complement component 1, q subcomponent, B chain (C1QB),
fibrinogen beta chain (FIBB or FIB), C-reactive protein (CRP),
inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), chorionic
somatomammotropin hormone (CSH), and angiotensinogen (ANG or ANGT).
In some embodiments, the invention provides a biomarker panel
comprising Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0056] In another aspect, the invention provides a biomarker panel
comprising at least two isolated biomarkers selected from the group
consisting of lipopolysaccharide-binding protein (LBP), prothrombin
(THRB), complement component C5 (C5 or CO5), plasminogen (PLMN),
complement component C8 gamma chain (C8G or CO8G), complement
component 1, q subcomponent, B chain (C1QB), fibrinogen beta chain
(FIBB or FIB), C-reactive protein (CRP), inter-alpha-trypsin
inhibitor heavy chain H4 (ITIH4), chorionic somatomammotropin
hormone (CSH), and angiotensinogen (ANG or ANGT) and the biomarkers
set forth in Tables 51 and 53.
[0057] In another aspect, the invention provides a biomarker panel
comprising at least two isolated biomarkers selected from the group
consisting of Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0058] It must be noted that, as used in this specification and the
appended claims, the singular forms "a", "an" and "the" include
plural referents unless the content clearly dictates otherwise.
Thus, for example, reference to "a biomarker" includes a mixture of
two or more biomarkers, and the like.
[0059] The term "about," particularly in reference to a given
quantity, is meant to encompass deviations of plus or minus five
percent.
[0060] As used in this application, including the appended claims,
the singular forms "a," "an," and "the" include plural references,
unless the content clearly dictates otherwise, and are used
interchangeably with "at least one" and "one or more."
[0061] As used herein, the terms "comprises," "comprising,"
"includes," "including," "contains," "containing," and any
variations thereof, are intended to cover a non-exclusive
inclusion, such that a process, method, product-by-process, or
composition of matter that comprises, includes, or contains an
element or list of elements does not include only those elements
but can include other elements not expressly listed or inherent to
such process, method, product-by-process, or composition of
matter.
[0062] As used herein, the term "panel" refers to a composition,
such as an array or a collection, comprising one or more
biomarkers. The term can also refer to a profile or index of
expression patterns of one or more biomarkers described herein. The
number of biomarkers useful for a biomarker panel is based on the
sensitivity and specificity value for the particular combination of
biomarker values.
[0063] As used herein, and unless otherwise specified, the terms
"isolated" and "purified" generally describes a composition of
matter that has been removed from its native environment (e.g., the
natural environment if it is naturally occurring), and thus is
altered by the hand of man from its natural state. An isolated
protein or nucleic acid is distinct from the way it exists in
nature.
[0064] The term "biomarker" refers to a biological molecule, or a
fragment of a biological molecule, the change and/or the detection
of which can be correlated with a particular physical condition or
state. The terms "marker" and "biomarker" are used interchangeably
throughout the disclosure. For example, the biomarkers of the
present invention are correlated with an increased likelihood of
preterm birth. Such biomarkers include, but are not limited to,
biological molecules comprising nucleotides, nucleic acids,
nucleosides, amino acids, sugars, fatty acids, steroids,
metabolites, peptides, polypeptides, proteins, carbohydrates,
lipids, hormones, antibodies, regions of interest that serve as
surrogates for biological macromolecules and combinations thereof
(e.g., glycoproteins, ribonucleoproteins, lipoproteins). The term
also encompasses portions or fragments of a biological molecule,
for example, peptide fragment of a protein or polypeptide that
comprises at least 5 consecutive amino acid residues, at least 6
consecutive amino acid residues, at least 7 consecutive amino acid
residues, at least 8 consecutive amino acid residues, at least 9
consecutive amino acid residues, at least 10 consecutive amino acid
residues, at least 11 consecutive amino acid residues, at least 12
consecutive amino acid residues, at least 13 consecutive amino acid
residues, at least 14 consecutive amino acid residues, at least 15
consecutive amino acid residues, at least 5 consecutive amino acid
residues, at least 16 consecutive amino acid residues, at least 17
consecutive amino acid residues, at least 18 consecutive amino acid
residues, at least 19 consecutive amino acid residues, at least 20
consecutive amino acid residues, at least 21 consecutive amino acid
residues, at least 22 consecutive amino acid residues, at least 23
consecutive amino acid residues, at least 24 consecutive amino acid
residues, at least 25 consecutive amino acid residues,or more
consecutive amino acid residues.
[0065] The invention also provides a method of determining
probability for preterm birth in a pregnant female, the method
comprising detecting a measurable feature of each of N biomarkers
selected from the biomarkers listed in Tables 1 through 63 in a
biological sample obtained from the pregnant female, and analyzing
the measurable feature to determine the probability for preterm
birth in the pregnant female. As disclosed herein, a measurable
feature comprises fragments or derivatives of each of said N
biomarkers selected from the biomarkers listed in Tables 1 through
63. In some embodiments of the disclosed methods detecting a
measurable feature comprises quantifying an amount of each of N
biomarkers selected from the biomarkers listed in Tables 1 through
63, combinations or portions and/or derivatives thereof in a
biological sample obtained from said pregnant female.
[0066] The invention further provides a method of predicting GAB,
the method encompassing detecting a measurable feature of each of N
biomarkers selected from the biomarkers listed in Tables 1 through
63 in a biological sample obtained from a pregnant female, and
analyzing the measurable feature to predict GAB.
[0067] The invention also provides a method of prediciting GAB, the
method comprising: (a) quantifying in a biological sample obtained
from the pregnant female an amount of each of N biomarkers selected
from the biomarkers listed in Tables 1 through 63; (b) multiplying
or thresholding the amount by a predetermined coefficient, (c)
determining the predicted GAB birth in the pregnant female
comprising adding the individual products to obtain a total risk
score that corresponds to the predicted GAB.
[0068] The invention further provides a method of prediciting time
to birth in a pregnant female, the method comprising: (a) obtaining
a biological sample from the pregnant female; (b) quantifying an
amount of each of N biomarkers selected from the biomarkers listed
in Tables 1 through 63 in the biological sample; (c) multiplying or
thresholding the amount by a predetermined coefficient, (d)
determining predicted GAB in the pregnant female comprising adding
the individual products to obtain a total risk score that
corresponds to the predicted GAB; and (e) substracting the
estimated gestational age (GA) at time biological sample was
obtained from the predicted GAB to predict time to birth in said
pregnant female. For methods directed to prediciting time to birth,
it is understood that "birth" means birth following spontaneous
onset of labor, with or without rupture of membranes.
[0069] Although described and exemplified with reference to methods
of determining probability for preterm birth in a pregnant female,
the present disclosure is similarly applicable to the methods of
predicting GAB, the methods for predicting term birth, methods for
determining the probability of term birth in a pregnant female as
well methods of prediciting time to birth in a pregnant female. It
will be apparent to one skilled in the art that each of the
aforementioned methods has specific and substantial utilities and
benefits with regard maternal-fetal health considerations.
[0070] In some embodiments, the method of determining probability
for preterm birth in a pregnant female and related methods
disclosed herein comprise detecting a measurable feature of each of
N biomarkers, wherein N is selected from the group consisting of 2
to 24. In further embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of AFTECCVVASQLR, ELLESYIDGR, and ITLPDFTGDLR. In
further embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of FLNWIK, FGFGGSTDSGPIR, LLELTGPK, VEHSDLSFSK,
IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER, DVLLLVHNLPQNLPGYFWYK,
SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK, and LSETNR.
[0071] In additional embodiments, the disclosed methods of
determining probability for preterm birth in a pregnant female and
related methods disclosed herein comprise detecting a measurable
feature of each of at least two isolated biomarkers selected from
the group consisting of the biomarkers set forth in Table 50 and
the biomarkers set forth in Table 52.
[0072] In additional embodiments, the method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of lipopolysaccharide-binding protein (LBP), prothrombin
(THRB), complement component C5 (C5 or CO5), plasminogen (PLMN),
and complement component C8 gamma chain (C8G or CO8G).
[0073] In additional embodiments, the method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0074] In further embodiments, the disclosed method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of lipopolysaccharide-binding protein (LBP), prothrombin
(THRB), complement component C5 (C5 or CO5), plasminogen (PLMN),
complement component C8 gamma chain (C8G or CO8G), complement
component 1, q subcomponent, B chain (C1QB), fibrinogen beta chain
(FIBB or FIB), C-reactive protein (CRP), inter-alpha-trypsin
inhibitor heavy chain H4 (ITIH4), chorionic somatomammotropin
hormone (CSH), and angiotensinogen (ANG or ANGT).
[0075] In further embodiments, the disclosed method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0076] In further embodiments, the disclosed method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of Alpha-1B-glycoprotein (A1BG), Disintegrin and
metalloproteinase domain-containing protein 12 (ADA12),
Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0077] In further embodiments, the disclosed method of determining
probability for preterm birth in a pregnant female and related
methods disclosed herein comprise detecting a measurable feature of
each of at least two isolated biomarkers selected from the group
consisting of the biomarkers set forth in Table 51 and the
biomarkers set forth in Table 53.
[0078] In additional embodiments, the methods of determining
probability for preterm birth in a pregnant female further
encompass detecting a measurable feature for one or more risk
indicia associated with preterm birth. In additional embodiments
the risk indicia are selected form the group consisting of previous
low birth weight or preterm delivery, multiple 2nd trimester
spontaneous abortions, prior first trimester induced abortion,
familial and intergenerational factors, history of infertility,
nulliparity, placental abnormalities, cervical and uterine
anomalies, gestational bleeding, intrauterine growth restriction,
in utero diethylstilbestrol exposure, multiple gestations, infant
sex, short stature, low prepregnancy weight, low or high body mass
index, diabetes, hypertension, and urogenital infections.
[0079] A "measurable feature" is any property, characteristic or
aspect that can be determined and correlated with the probability
for preterm birth in a subject. The term further encompasses any
property, characteristic or aspect that can be determined and
correlated in connection with a prediction of GAB, a prediction of
term birth, or a prediction of time to birth in a pregnant female.
For a biomarker, such a measurable feature can include, for
example, the presence, absence, or concentration of the biomarker,
or a fragment thereof, in the biological sample, an altered
structure, such as, for example, the presence or amount of a
post-translational modification, such as oxidation at one or more
positions on the amino acid sequence of the biomarker or, for
example, the presence of an altered conformation in comparison to
the conformation of the biomarker in normal control subjects,
and/or the presence, amount, or altered structure of the biomarker
as a part of a profile of more than one biomarker. In addition to
biomarkers, measurable features can further include risk indicia
including, for example, maternal characteristics, age, race,
ethnicity, medical history, past pregnancy history, obstetrical
history. For a risk indicium, a measurable feature can include, for
example, previous low birth weight or preterm delivery, multiple
2nd trimester spontaneous abortions, prior first trimester induced
abortion, familial and intergenerational factors, history of
infertility, nulliparity, placental abnormalities, cervical and
uterine anomalies, short cervical length meansurements, gestational
bleeding, intrauterine growth restriction, in utero
diethylstilbestrol exposure, multiple gestations, infant sex, short
stature, low prepregnancy weight/low body mass index, diabetes,
hypertension, urogenital infections, hypothyroidism,asthma, low
educational attainment, cigarette smoking, drug use and alcohol
consumption.
[0080] In some embodiments of the disclosed methods of determining
probability for preterm birth in a pregnant female, the probability
for preterm birth in the pregnant female is calculated based on the
quantified amount of each of N biomarkers selected from the
biomarkers listed in Tables 1 through 63. In some embodiments, the
disclosed methods for determining the probability of preterm birth
encompass detecting and/or quantifying one or more biomarkers using
mass sprectrometry, a capture agent or a combination thereof
[0081] In some embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass an
initial step of providing a biomarker panel comprising N of the
biomarkers listed in Tables 1 through 63. In additional
embodiments, the disclosed methods of determining probability for
preterm birth in a pregnant female encompass an initial step of
providing a biological sample from the pregnant female.
[0082] In some embodiments, the disclosed methods of determining
probability for preterm birth in a pregnant female encompass
communicating the probability to a health care provider. The
disclosed of predicting GAB, the methods for predicting term birth,
methods for determining the probability of term birth in a pregnant
female as well methods of prediciting time to birth in a pregnant
female similarly encompass communicating the probability to a
health care provider. As stated above, although described and
exemplified with reference to determining probability for preterm
birth in a pregnant female, all embodiments described throughout
this disclosure are similarly applicable to the methods of
predicting GAB, the methods for predicting term birth, methods for
determining the probability of term birth in a pregnant female as
well methods of prediciting time to birth in a pregnant female.
Specifically, he biomarkers and panels recited throughout this
application with express reference to methods for preterm birth can
also be used in methods for predicting GAB, the methods for
predicting term birth, methods for determining the probability of
term birth in a pregnant female as well methods of prediciting time
to birth in a pregnant female. It will be apparent to one skilled
in the art that each of the aforementioned methods have specific
and substantial utilities and benefits with regard maternal-fetal
health considerations.
[0083] In additional embodiments, the communication informs a
subsequent treatment decision for the pregnant female. In some
embodiments, the method of determining probability for preterm
birth in a pregnant female encompasses the additional feature of
expressing the probability as a risk score.
[0084] As used herein, the term "risk score" refers to a score that
can be assigned based on comparing the amount of one or more
biomarkers in a biological sample obtained from a pregnant female
to a standard or reference score that represents an average amount
of the one or more biomarkers calculated from biological samples
obtained from a random pool of pregnant females. Because the level
of a biomarker may not be static throughout pregnancy, a standard
or reference score has to have been obtained for the gestational
time point that corresponds to that of the pregnant female at the
time the sample was taken. The standard or reference score can be
predetermined and built into a predictor model such that the
comparison is indirect rather than actually performed every time
the probability is determined for a subject. A risk score can be a
standard (e.g., a number) or a threshold (e.g., a line on a graph).
The value of the risk score correlates to the deviation, upwards or
downwards, from the average amount of the one or more biomarkers
calculated from biological samples obtained from a random pool of
pregnant females. In certain embodiments, if a risk score is
greater than a standard or reference risk score, the pregnant
female can have an increased likelihood of preterm birth. In some
embodiments, the magnitude of a pregnant female's risk score, or
the amount by which it exceeds a reference risk score, can be
indicative of or correlated to that pregnant female's level of
risk.
[0085] In the context of the present invention, the term
"biological sample," encompasses any sample that is taken from
pregnant female and contains one or more of the biomarkers listed
in Tables 1 through 63. Suitable samples in the context of the
present invention include, for example, blood, plasma, serum,
amniotic fluid, vaginal secretions, saliva, and urine. In some
embodiments, the biological sample is selected from the group
consisting of whole blood, plasma, and serum. In a particular
embodiment, the biological sample is serum. As will be appreciated
by those skilled in the art, a biological sample can include any
fraction or component of blood, without limitation, T cells,
monocytes, neutrophils, erythrocytes, platelets and microvesicles
such as exosomes and exosome-like vesicles. In a particular
embodiment, the biological sample is serum.
[0086] Preterm birth refers to delivery or birth at a gestational
age less than 37 completed weeks. Other commonly used subcategories
of preterm birth have been established and delineate moderately
preterm (birth at 33 to 36 weeks of gestation), very preterm (birth
at <33 weeks of gestation), and extremely preterm (birth at
<28 weeks of gestation). With regard to the methods disclosed
herein, those skilled in the art understand that the cut-offs that
delineate preterm birth and term birth as well as the cut-offs that
delineate subcategories of preterm birth can be adjusted in
practicing the methods disclosed herein, for example, to maximize a
particular health benefit. It is further understood that such
adjustments are well within the skill set of individuals considered
skilled in the art and encompassed within the scope of the
inventions disclosed herein. Gestational age is a proxy for the
extent of fetal development and the fetus's readiness for birth.
Gestational age has typically been defined as the length of time
from the date of the last normal menses to the date of birth.
However, obstetric measures and ultrasound estimates also can aid
in estimating gestational age. Preterm births have generally been
classified into two separate subgroups. One, spontaneous preterm
births are those occurring subsequent to spontaneous onset of
preterm labor or preterm premature rupture of membranes regardless
of subsequent labor augmentation or cesarean delivery. Two,
indicated preterm births are those occurring following induction or
cesarean section for one or more conditions that the woman's
caregiver determines to threaten the health or life of the mother
and/or fetus. In some embodiments, the methods disclosed herein are
directed to determining the probability for spontaneous preterm
birth. In additional embodiments, the methods disclosed herein are
directed to predicting gestational birth.
[0087] As used herein, the term "estimated gestational age" or
"estimated GA" refers to the GA determined based on the date of the
last normal menses and additional obstetric measures, ultrasound
estimates or other clinical parameters including, without
limitation, those described in the preceding paragraph. In contrast
the term "predicted gestational age at birth" or "predicted GAB"
refers to the GAB determined based on the methods of the invention
as dislosed herein. As used herein, "term birth" refers to birth at
a gestational age equal or more than 37 completed weeks.
[0088] In some embodiments, the pregnant female is between 17 and
28 weeks of gestation at the time the biological sample is
collected. In other embodiments, the pregnant female is between 16
and 29 weeks, between 17 and 28 weeks, between 18 and 27 weeks,
between 19 and 26 weeks, between 20 and 25 weeks, between 21 and 24
weeks, or between 22 and 23 weeks of gestation at the time the
biological sample is collected. In further embodiments, the
pregnant female is between about 17 and 22 weeks, between about 16
and 22 weeks between about 22 and 25 weeks, between about 13 and 25
weeks, between about 26 and 28, or between about 26 and 29 weeks of
gestation at the time the biological sample is collected.
Accordingly, the gestational age of a pregnant female at the time
the biological sample is collected can be 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 weeks.
[0089] In some embodiments of the claimed methods the measurable
feature comprises fragments or derivatives of each of the N
biomarkers selected from the biomarkers listed in Tables 1 through
63. In additional embodiments of the claimed methods, detecting a
measurable feature comprises quantifying an amount of each of N
biomarkers selected from the biomarkers listed in Tables 1 through
63, combinations or portions and/or derivatives thereof in a
biological sample obtained from said pregnant female.
[0090] The term "amount" or "level" as used herein refers to a
quantity of a biomarker that is detectable or measurable in a
biological sample and/or control. The quantity of a biomarker can
be, for example, a quantity of polypeptide, the quantity of nucleic
acid, or the quantity of a fragment or surrogate. The term can
alternatively include combinations thereof. The term "amount" or
"level" of a biomarker is a measurable feature of that
biomarker.
[0091] In some embodiments, calculating the probability for preterm
birth in a pregnant female is based on the quantified amount of
each of N biomarkers selected from the biomarkers listed in Tables
1 through 63. Any existing, available or conventional separation,
detection and quantification methods can be used herein to measure
the presence or absence (e.g., readout being present vs. absent; or
detectable amount vs. undetectable amount) and/or quantity (e.g.,
readout being an absolute or relative quantity, such as, for
example, absolute or relative concentration) of biomarkers,
peptides, polypeptides, proteins and/or fragments thereof and
optionally of the one or more other biomarkers or fragments thereof
in samples. In some embodiments, detection and/or quantification of
one or more biomarkers comprises an assay that utilizes a capture
agent. In further embodiments, the capture agent is an antibody,
antibody fragment, nucleic acid-based protein binding reagent,
small molecule or variant thereof. In additional embodiments, the
assay is an enzyme immunoassay (EIA), enzyme-linked immunosorbent
assay (ELISA), and radioimmunoassay (RIA). In some embodiments,
detection and/or quantification of one or more biomarkers further
comprises mass spectrometry (MS). In yet further embodiments, the
mass spectrometry is co-immunoprecitipation-mass spectrometry
(co-IP MS), where coimmunoprecipitation, a technique suitable for
the isolation of whole protein complexes is followed by mass
spectrometric analysis.
[0092] As used herein, the term "mass spectrometer" refers to a
device able to volatilize/ionize analytes to form gas-phase ions
and determine their absolute or relative molecular masses. Suitable
methods of volatilization/ionization are matrix-assisted laser
desorption ionization (MALDI), electrospray, laser/light, thermal,
electrical, atomized/sprayed and the like, or combinations thereof.
Suitable forms of mass spectrometry include, but are not limited
to, ion trap instruments, quadrupole instruments, electrostatic and
magnetic sector instruments, time of flight instruments, time of
flight tandem mass spectrometer (TOF MS/MS), Fourier-transform mass
spectrometers, Orbitraps and hybrid instruments composed of various
combinations of these types of mass analyzers. These instruments
can, in turn, be interfaced with a variety of other instruments
that fractionate the samples (for example, liquid chromatography or
solid-phase adsorption techniques based on chemical, or biological
properties) and that ionize the samples for introduction into the
mass spectrometer, including matrix-assisted laser desorption
(MALDI), electrospray, or nanospray ionization (ESI) or
combinations thereof.
[0093] Generally, any mass spectrometric (MS) technique that can
provide precise information on the mass of peptides, and preferably
also on fragmentation and/or (partial) amino acid sequence of
selected peptides (e.g., in tandem mass spectrometry, MS/MS; or in
post source decay, TOF MS), can be used in the methods disclosed
herein. Suitable peptide MS and MS/MS techniques and systems are
well-known per se (see, e.g., Methods in Molecular Biology, vol.
146: "Mass Spectrometry of Proteins and Peptides", by Chapman, ed.,
Humana Press 2000; Biemann 1990. Methods Enzymol 193: 455-79; or
Methods in Enzymology, vol. 402: "Biological Mass Spectrometry", by
Burlingame, ed., Academic Press 2005) and can be used in practicing
the methods disclosed herein. Accordingly, in some embodiments, the
disclosed methods comprise performing quantitative MS to measure
one or more biomarkers. Such quantitiative methods can be performed
in an automated (Villanueva, et al., Nature Protocols (2006)
1(2):880-891) or semi-automated format. In particular embodiments,
MS can be operably linked to a liquid chromatography device
(LC-MS/MS or LC-MS) or gas chromatography device (GC-MS or
GC-MS/MS). Other methods useful in this context include
isotope-coded affinity tag (ICAT), tandem mass tags (TMT), or
stable isotope labeling by amino acids in cell culture (SILAC),
followed by chromatography and MS/MS.
[0094] As used herein, the terms "multiple reaction monitoring
(MRM)" or "selected reaction monitoring (SRM)" refer to an MS-based
quantification method that is particularly useful for quantifying
analytes that are in low abundance. In an SRM experiment, a
predefined precursor ion and one or more of its fragments are
selected by the two mass filters of a triple quadrupole instrument
and monitored over time for precise quantification. Multiple SRM
precursor and fragment ion pairs can be measured within the same
experiment on the chromatographic time scale by rapidly toggling
between the different precursor/fragment pairs to perform an MRM
experiment. A series of transitions (precursor/fragment ion pairs)
in combination with the retention time of the targeted analyte
(e.g., peptide or small molecule such as chemical entity, steroid,
hormone) can constitute a definitive assay. A large number of
analytes can be quantified during a single LC-MS experiment. The
term "scheduled," or "dynamic" in reference to MRM or SRM, refers
to a variation of the assay wherein the transitions for a
particular analyte are only acquired in a time window around the
expected retention time, significantly increasing the number of
analytes that can be detected and quantified in a single LC-MS
experiment and contributing to the selectivity of the test, as
retention time is a property dependent on the physical nature of
the analyte. A single analyte can also be monitored with more than
one transition. Finally, included in the assay can be standards
that correspond to the analytes of interest (e.g., same amino acid
sequence), but differ by the inclusion of stable isotopes. Stable
isotopic standards (SIS) can be incorporated into the assay at
precise levels and used to quantify the corresponding unknown
analyte. An additional level of specificity is contributed by the
co-elution of the unknown analyte and its corresponding SIS and
properties of their transitions (e.g., the similarity in the ratio
of the level of two transitions of the unknown and the ratio of the
two transitions of its corresponding SIS).
[0095] Mass spectrometry assays, instruments and systems suitable
for biomarker peptide analysis can include, without limitation,
matrix-assisted laser desorption/ionisation time-of-flight
(MALDI-TOF) MS; MALDI-TOF post-source-decay (PSD); MALDI-TOF/TOF;
surface-enhanced laser desorption/ionization time-of-flight mass
spectrometry (SELDI-TOF) MS; electrospray ionization mass
spectrometry (ESI-MS); ESI-MS/MS; ESI-MS/(MS).sub.n (n is an
integer greater than zero); ESI 3D or linear (2D) ion trap MS; ESI
triple quadrupole MS; ESI quadrupole orthogonal TOF (Q-TOF); ESI
Fourier transform MS systems; desorption/ionization on silicon
(DIOS); secondary ion mass spectrometry (SIMS); atmospheric
pressure chemical ionization mass spectrometry (APCI-MS);
APCI-MS/MS; APCI-(MS).sub.n; ion mobility spectrometry (IMS);
inductively coupled plasma mass spectrometry (ICP-MS)atmospheric
pressure photoionization mass spectrometry (APPI-MS); APPI-MS/MS;
and APPI-(MS).sub.n. Peptide ion fragmentation in tandem MS (MS/MS)
arrangements can be achieved using manners established in the art,
such as, e.g., collision induced dissociation (CID). As described
herein, detection and quantification of biomarkers by mass
spectrometry can involve multiple reaction monitoring (MRM), such
as described among others by Kuhn et al. Proteomics 4: 1175-86
(2004). Scheduled multiple-reaction-monitoring (Scheduled MRM) mode
acquisition during LC-MS/MS analysis enhances the sensitivity and
accuracy of peptide quantitation. Anderson and Hunter, Molecular
and Cellular Proteomics 5(4):573 (2006). As described herein, mass
spectrometry-based assays can be advantageously combined with
upstream peptide or protein separation or fractionation methods,
such as for example with the chromatographic and other methods
described herein below. As further described herein, shotgun
quantitative proteomics can be combined with SRM/MRM-based assays
for high-throughput identification and verification of prognostic
biomarkers of preterm birth.
[0096] A person skilled in the art will appreciate that a number of
methods can be used to determine the amount of a biomarker,
including mass spectrometry approaches, such as MS/MS, LC-MS/MS,
multiple reaction monitoring (MRM) or SRM and product-ion
monitoring (PIM) and also including antibody based methods such as
immunoassays such as Western blots, enzyme-linked immunosorbant
assay (ELISA), immunopercipitation, immunohistochemistry,
immunofluorescence, radioimmunoassay, dot blotting, and FACS.
Accordingly, in some embodiments, determining the level of the at
least one biomarker comprises using an immunoassay and/or mass
spectrometric methods. In additional embodiments, the mass
spectrometric methods are selected from MS, MS/MS, LC-MS/MS, SRM,
PIM, and other such methods that are known in the art. In other
embodiments, LC-MS/MS further comprises 1D LC-MS/MS, 2D LC-MS/MS or
3D LC-MS/MS. Immunoassay techniques and protocols are generally
known to those skilled in the art (Price and Newman, Principles and
Practice of Immunoassay, 2nd Edition, Grove's Dictionaries, 1997;
and Gosling, Immunoassays: A Practical Approach, Oxford University
Press, 2000.) A variety of immunoassay techniques, including
competitive and non-competitive immunoassays, can be used (Self et
al., Curr. Opin. Biotechnol., 7:60-65 (1996).
[0097] In further embodiments, the immunoassay is selected from
Western blot, ELISA, immunoprecipitation, immunohistochemistry,
immunofluorescence, radioimmunoassay (RIA), dot blotting, and FACS.
In certain embodiments, the immunoassay is an ELISA. In yet a
further embodiment, the ELISA is direct ELISA (enzyme-linked
immunosorbent assay), indirect ELISA, sandwich ELISA, competitive
ELISA, multiplex ELISA, ELISPOT technologies, and other similar
techniques known in the art. Principles of these immunoassay
methods are known in the art, for example John R. Crowther, The
ELISA Guidebook, 1st ed., Humana Press 2000, ISBN 0896037282.
Typically ELISAs are performed with antibodies but they can be
performed with any capture agents that bind specifically to one or
more biomarkers of the invention and that can be detected.
Multiplex ELISA allows simultaneous detection of two or more
analytes within a single compartment (e.g., microplate well)
usually at a plurality of array addresses (Nielsen and Geierstanger
2004. J Immunol Methods 290: 107-20 (2004) and Ling et al. 2007.
Expert Rev Mol Diagn 7: 87-98 (2007)).
[0098] In some embodiments, Radioimmunoassay (RIA) can be used to
detect one or more biomarkers in the methods of the invention. RIA
is a competition-based assay that is well known in the art and
involves mixing known quantities of radioactavely-labelled (e.g.,
.sup.125I or .sup.131I-labelled) target analyte with antibody
specific for the analyte, then adding non-labelled analyte from a
sample and measuring the amount of labelled analyte that is
displaced (see, e.g., An Introduction to Radioimmunoassay and
Related Techniques, by Chard T, ed., Elsevier Science 1995, ISBN
0444821198 for guidance).
[0099] A detectable label can be used in the assays described
herein for direct or indirect detection of the biomarkers in the
methods of the invention. A wide variety of detectable labels can
be used, with the choice of label depending on the sensitivity
required, ease of conjugation with the antibody, stability
requirements, and available instrumentation and disposal
provisions. Those skilled in the art are familiar with selection of
a suitable detectable label based on the assay detection of the
biomarkers in the methods of the invention. Suitable detectable
labels include, but are not limited to, fluorescent dyes (e.g.,
fluorescein, fluorescein isothiocyanate (FITC), Oregon Green.TM.,
rhodamine, Texas red, tetrarhodimine isothiocynate (TRITC), Cy3,
Cy5, etc.), fluorescent markers (e.g., green fluorescent protein
(GFP), phycoerythrin, etc.), enzymes (e.g., luciferase, horseradish
peroxidase, alkaline phosphatase, etc.), nanoparticles, biotin,
digoxigenin, metals, and the like.
[0100] For mass-sectrometry based analysis, differential tagging
with isotopic reagents, e.g., isotope-coded affinity tags (ICAT) or
the more recent variation that uses isobaric tagging reagents,
iTRAQ (Applied Biosystems, Foster City, Calif.), or tandem mass
tags, TMT, (Thermo Scientific, Rockford, Ill.), followed by
multidimensional liquid chromatography (LC) and tandem mass
spectrometry (MS/MS) analysis can provide a further methodology in
practicing the methods of the inventon.
[0101] A chemiluminescence assay using a chemiluminescent antibody
can be used for sensitive, non-radioactive detection of protein
levels. An antibody labeled with fluorochrome also can be suitable.
Examples of fluorochromes include, without limitation, DAPI,
fluorescein, Hoechst 33258, R-phycocyanin, B-phycoerythrin,
R-phycoerythrin, rhodamine, Texas red, and lissamine. Indirect
labels include various enzymes well known in the art, such as
horseradish peroxidase (HRP), alkaline phosphatase (AP),
beta-galactosidase, urease, and the like. Detection systems using
suitable substrates for horseradish-peroxidase, alkaline
phosphatase, beta-galactosidase are well known in the art.
[0102] A signal from the direct or indirect label can be analyzed,
for example, using a spectrophotometer to detect color from a
chromogenic substrate; a radiation counter to detect radiation such
as a gamma counter for detection of .sup.125I; or a fluorometer to
detect fluorescence in the presence of light of a certain
wavelength. For detection of enzyme-linked antibodies, a
quantitative analysis can be made using a spectrophotometer such as
an EMAX Microplate Reader (Molecular Devices; Menlo Park, Calif.)
in accordance with the manufacturer's instructions. If desired,
assays used to practice the invention can be automated or performed
robotically, and the signal from multiple samples can be detected
simultaneously.
[0103] In some embodiments, the methods described herein encompass
quantification of the biomarkers using mass spectrometry (MS). In
further embodiments, the mass spectrometry can be liquid
chromatography-mass spectrometry (LC-MS), multiple reaction
monitoring (MRM) or selected reaction monitoring (SRM). In
additional embodiments, the MRM or SRM can further encompass
scheduled MRM or scheduled SRM.
[0104] As described above, chromatography can also be used in
practicing the methods of the invention. Chromatography encompasses
methods for separating chemical substances and generally involves a
process in which a mixture of analytes is carried by a moving
stream of liquid or gas ("mobile phase") and separated into
components as a result of differential distribution of the analytes
as they flow around or over a stationary liquid or solid phase
("stationary phase"), between the mobile phase and said stationary
phase. The stationary phase can be usually a finely divided solid,
a sheet of filter material, or a thin film of a liquid on the
surface of a solid, or the like. Chromatography is well understood
by those skilled in the art as a technique applicable for the
separation of chemical compounds of biological origin, such as,
e.g., amino acids, proteins, fragments of proteins or peptides,
etc.
[0105] Chromatography can be columnar (i.e., wherein the stationary
phase is deposited or packed in a column), preferably liquid
chromatography, and yet more preferably high-performance liquid
chromatography (HPLC), or ultra high performance/pressure liquid
chromatography (UHPLC). Particulars of chromatography are well
known in the art (Bidlingmeyer, Practical HPLC Methodology and
Applications, John Wiley & Sons Inc., 1993). Exemplary types of
chromatography include, without limitation, high-performance liquid
chromatography (HPLC), UHPLC, normal phase HPLC (NP-HPLC), reversed
phase HPLC (RP-HPLC), ion exchange chromatography (IEC), such as
cation or anion exchange chromatography, hydrophilic interaction
chromatography (HILIC), hydrophobic interaction chromatography
(HIC), size exclusion chromatography (SEC) including gel filtration
chromatography or gel permeation chromatography, chromatofocusing,
affinity chromatography such as immuno-affinity, immobilised metal
affinity chromatography, and the like. Chromatography, including
single-, two- or more-dimensional chromatography, can be used as a
peptide fractionation method in conjunction with a further peptide
analysis method, such as for example, with a downstream mass
spectrometry analysis as described elsewhere in this
specification.
[0106] Further peptide or polypeptide separation, identification or
quantification methods can be used, optionally in conjunction with
any of the above described analysis methods, for measuring
biomarkers in the present disclosure. Such methods include, without
limitation, chemical extraction partitioning, isoelectric focusing
(IEF) including capillary isoelectric focusing (CIEF), capillary
isotachophoresis (CITP), capillary electrochromatography (CEC), and
the like, one-dimensional polyacrylamide gel electrophoresis
(PAGE), two-dimensional polyacrylamide gel electrophoresis
(2D-PAGE), capillary gel electrophoresis (CGE), capillary zone
electrophoresis (CZE), micellar electrokinetic chromatography
(MEKC), free flow electrophoresis (FFE), etc.
[0107] In the context of the invention, the term "capture agent"
refers to a compound that can specifically bind to a target, in
particular a biomarker. The term includes antibodies, antibody
fragments, nucleic acid-based protein binding reagents (e.g.
aptamers, Slow Off-rate Modified Aptamers (SOMAmer.TM.)),
protein-capture agents, natural ligands (i.e. a hormone for its
receptor or vice versa), small molecules or variants thereof.
[0108] Capture agents can be configured to specifically bind to a
target, in particular a biomarker. Capture agents can include but
are not limited to organic molecules, such as polypeptides,
polynucleotides and other non polymeric molecules that are
identifiable to a skilled person. In the embodiments disclosed
herein, capture agents include any agent that can be used to
detect, purify, isolate, or enrich a target, in particular a
biomarker. Any art-known affinity capture technologies can be used
to selectively isolate and enrich/concentrate biomarkers that are
components of complex mixtures of biological media for use in the
disclosed methods.
[0109] Antibody capture agents that specifically bind to a
biomarker can be prepared using any suitable methods known in the
art. See, e.g., Coligan, Current Protocols in Immunology (1991);
Harlow & Lane, Antibodies: A Laboratory Manual (1988); Goding,
Monoclonal Antibodies: Principles and Practice (2d ed. 1986).
Antibody capture agents can be any immunoglobulin or derivative
therof, whether natural or wholly or partially synthetically
produced. All derivatives thereof which maintain specific binding
ability are also included in the term. Antibody capture agents have
a binding domain that is homologous or largely homologous to an
immunoglobulin binding domain and can be derived from natural
sources, or partly or wholly synthetically produced. Antibody
capture agents can be monoclonal or polyclonal antibodies. In some
embodiments, an antibody is a single chain antibody. Those of
ordinary skill in the art will appreciate that antibodies can be
provided in any of a variety of forms including, for example,
humanized, partially humanized, chimeric, chimeric humanized, etc.
Antibody capture agents can be antibody fragments including, but
not limited to, Fab, Fab', F(ab')2, scFv, Fv, dsFv diabody, and Fd
fragments. An antibody capture agent can be produced by any means.
For example, an antibody capture agent can be enzymatically or
chemically produced by fragmentation of an intact antibody and/or
it can be recombinantly produced from a gene encoding the partial
antibody sequence. An antibody capture agent can comprise a single
chain antibody fragment. Alternatively or additionally, antibody
capture agent can comprise multiple chains which are linked
together, for example, by disulfide linkages; and, any functional
fragments obtained from such molecules, wherein such fragments
retain specific-binding properties of the parent antibody molecule.
Because of their smaller size as functional components of the whole
molecule, antibody fragments can offer advantages over intact
antibodies for use in certain immunochemical techniques and
experimental applications.
[0110] Suitable capture agents useful for practicing the invention
also include aptamers. Aptamers are oligonucleotide sequences that
can bind to their targets specifically via unique three dimensional
(3-D) structures. An aptamer can include any suitable number of
nucleotides and different aptamers can have either the same or
different numbers of nucleotides. Aptamers can be DNA or RNA or
chemically modified nucleic acids and can be single stranded,
double stranded, or contain double stranded regions, and can
include higher ordered structures. An aptamer can also be a
photoaptamer, where a photoreactive or chemically reactive
functional group is included in the aptamer to allow it to be
covalently linked to its corresponding target. Use of an aptamer
capture agent can include the use of two or more aptamers that
specifically bind the same biomarker. An aptamer can include a tag.
An aptamer can be identified using any known method, including the
SELEX (systematic evolution of ligands by exponential enrichment),
process. Once identified, an aptamer can be prepared or synthesized
in accordance with any known method, including chemical synthetic
methods and enzymatic synthetic methods and used in a variety of
applications for biomarker detection. Liu et al., Curr Med Chem.
18(27):4117-25 (2011). Capture agents useful in practicing the
methods of the invention also include SOMAmers (Slow Off-Rate
Modified Aptamers) known in the art to have improved off-rate
characteristics. Brody et al., J Mol Biol. 422(5):595-606 (2012).
SOMAmers can be generated using any known method, including the
SELEX method.
[0111] It is understood by those skilled in the art that biomarkers
can be modified prior to analysis to improve their resolution or to
determine their identity. For example, the biomarkers can be
subject to proteolytic digestion before analysis. Any protease can
be used. Proteases, such as trypsin, that are likely to cleave the
biomarkers into a discrete number of fragments are particularly
useful. The fragments that result from digestion function as a
fingerprint for the biomarkers, thereby enabling their detection
indirectly. This is particularly useful where there are biomarkers
with similar molecular masses that might be confused for the
biomarker in question. Also, proteolytic fragmentation is useful
for high molecular weight biomarkers because smaller biomarkers are
more easily resolved by mass spectrometry. In another example,
biomarkers can be modified to improve detection resolution. For
instance, neuraminidase can be used to remove terminal sialic acid
residues from glycoproteins to improve binding to an anionic
adsorbent and to improve detection resolution. In another example,
the biomarkers can be modified by the attachment of a tag of
particular molecular weight that specifically binds to molecular
biomarkers, further distinguishing them. Optionally, after
detecting such modified biomarkers, the identity of the biomarkers
can be further determined by matching the physical and chemical
characteristics of the modified biomarkers in a protein database
(e.g., SwissProt).
[0112] It is further appreciated in the art that biomarkers in a
sample can be captured on a substrate for detection. Traditional
substrates include antibody-coated 96-well plates or nitrocellulose
membranes that are subsequently probed for the presence of the
proteins. Alternatively, protein-binding molecules attached to
microspheres, microparticles, microbeads, beads, or other particles
can be used for capture and detection of biomarkers. The
protein-binding molecules can be antibodies, peptides, peptoids,
aptamers, small molecule ligands or other protein-binding capture
agents attached to the surface of particles. Each protein-binding
molecule can include unique detectable label that is coded such
that it can be distinguished from other detectable labels attached
to other protein-binding molecules to allow detection of biomarkers
in multiplex assays. Examples include, but are not limited to,
color-coded microspheres with known fluorescent light intensities
(see e.g., microspheres with xMAP technology produced by Luminex
(Austin, Tex.); microspheres containing quantum dot nanocrystals,
for example, having different ratios and combinations of quantum
dot colors (e.g., Qdot nanocrystals produced by Life Technologies
(Carlsbad, Calif.); glass coated metal nanoparticles (see e.g.,
SERS nanotags produced by Nanoplex Technologies, Inc. (Mountain
View, Calif.); barcode materials (see e.g., sub-micron sized
striped metallic rods such as Nanobarcodes produced by Nanoplex
Technologies, Inc.), encoded microparticles with colored bar codes
(see e.g., CellCard produced by Vitra Bioscience, vitrabio.com),
glass microparticles with digital holographic code images (see
e.g., CyVera microbeads produced by Illumina (San Diego, Calif);
chemiluminescent dyes, combinations of dye compounds; and beads of
detectably different sizes.
[0113] In another aspect, biochips can be used for capture and
detection of the biomarkers of the invention. Many protein biochips
are known in the art. These include, for example, protein biochips
produced by Packard BioScience Company (Meriden Conn.), Zyomyx
(Hayward, Calif) and Phylos (Lexington, Mass.). In general, protein
biochips comprise a substrate having a surface. A capture reagent
or adsorbent is attached to the surface of the substrate.
Frequently, the surface comprises a plurality of addressable
locations, each of which location has the capture agent bound
there. The capture agent can be a biological molecule, such as a
polypeptide or a nucleic acid, which captures other biomarkers in a
specific manner. Alternatively, the capture agent can be a
chromatographic material, such as an anion exchange material or a
hydrophilic material. Examples of protein biochips are well known
in the art.
[0114] Measuring mRNA in a biological sample can be used as a
surrogate for detection of the level of the corresponding protein
biomarker in a biological sample. Thus, any of the biomarkers or
biomarker panels described herein can also be detected by detecting
the appropriate RNA. Levels of mRNA can measured by reverse
transcription quantitative polymerase chain reaction (RT-PCR
followed with qPCR). RT-PCR is used to create a cDNA from the mRNA.
The cDNA can be used in a qPCR assay to produce fluorescence as the
DNA amplification process progresses. By comparison to a standard
curve, qPCR can produce an absolute measurement such as number of
copies of mRNA per cell. Northern blots, microarrays, Invader
assays, and RT-PCR combined with capillary electrophoresis have all
been used to measure expression levels of mRNA in a sample. See
Gene Expression Profiling: Methods and Protocols, Richard A.
Shimkets, editor, Humana Press, 2004.
[0115] Some embodiments disclosed herein relate to diagnostic and
prognostic methods of determining the probability for preterm birth
in a pregnant female. The detection of the level of expression of
one or more biomarkers and/or the determination of a ratio of
biomarkers can be used to determine the probability for preterm
birth in a pregnant female. Such detection methods can be used, for
example, for early diagnosis of the condition, to determine whether
a subject is predisposed to preterm birth, to monitor the progress
of preterm birth or the progress of treatment protocols, to assess
the severity of preterm birth, to forecast the outcome of preterm
birth and/or prospects of recovery or birth at full term, or to aid
in the determination of a suitable treatment for preterm birth.
[0116] The quantitation of biomarkers in a biological sample can be
determined, without limitation, by the methods described above as
well as any other method known in the art. The quantitative data
thus obtained is then subjected to an analytic classification
process. In such a process, the raw data is manipulated according
to an algorithm, where the algorithm has been pre-defined by a
training set of data, for example as described in the examples
provided herein. An algorithm can utilize the training set of data
provided herein, or can utilize the guidelines provided herein to
generate an algorithm with a different set of data.
[0117] In some embodiments, analyzing a measurable feature to
determine the probability for preterm birth in a pregnant female
encompasses the use of a predictive model. In further embodiments,
analyzing a measurable feature to determine the probability for
preterm birth in a pregnant female encompasses comparing said
measurable feature with a reference feature. As those skilled in
the art can appreciate, such comparison can be a direct comparison
to the reference feature or an indirect comparison where the
reference feature has been incorporated into the predictive model.
In further embodiments, analyzing a measurable feature to determine
the probability for preterm birth in a pregnant female encompasses
one or more of a linear discriminant analysis model, a support
vector machine classification algorithm, a recursive feature
elimination model, a prediction analysis of microarray model, a
logistic regression model, a CART algorithm, a flex tree algorithm,
a LART algorithm, a random forest algorithm, a MART algorithm, a
machine learning algorithm, a penalized regression method, or a
combination thereof. In particular embodiments, the analysis
comprises logistic regression.
[0118] An analytic classification process can use any one of a
variety of statistical analytic methods to manipulate the
quantitative data and provide for classification of the sample.
Examples of useful methods include linear discriminant analysis,
recursive feature elimination, a prediction analysis of microarray,
a logistic regression, a CART algorithm, a FlexTree algorithm, a
LART algorithm, a random forest algorithm, a MART algorithm,
machine learning algorithms; etc.
[0119] For creation of a random forest for prediction of GAB one
skilled in the art can consider a set of k subjects (pregnant
women) for whom the gestational age at birth (GAB) is known, and
for whom N analytes (transitions) have been measured in a blood
specimen taken several weeks prior to birth. A regression tree
begins with a root node that contains all the subjects. The average
GAB for all subjects can be cacluclated in the root node. The
variance of the GAB within the root node will be high, because
there is a mixture of women with different GAB's. The root node is
then divided (partitioned) into two branches, so that each branch
contains women with a similar GAB. The average GAB for subjects in
each branch is again caluclated. The variance of the GAB within
each branch will be lower than in the root node, because the subset
of women within each branch has relatively more similar GAB's than
those in the root node. The two branches are created by selecting
an analyte and a threshold value for the analyte that creates
branches with similar GAB. The analyte and threshold value are
chosen from among the set of all analytes and threshold values,
usually with a random subset of the analytes at each node. The
procedure continues recursively producing branches to create leaves
(terminal nodes) in which the subjects have very similar GAB's. The
predicted GAB in each terminal node is the average GAB for subjects
in that terminal node. This procedure creates a single regression
tree. A random forest can consist of several hundred or several
thousand such trees.
[0120] Classification can be made according to predictive modeling
methods that set a threshold for determining the probability that a
sample belongs to a given class. The probability preferably is at
least 50%, or at least 60%, or at least 70%, or at least 80% or
higher. Classifications also can be made by determining whether a
comparison between an obtained dataset and a reference dataset
yields a statistically significant difference. If so, then the
sample from which the dataset was obtained is classified as not
belonging to the reference dataset class. Conversely, if such a
comparison is not statistically significantly different from the
reference dataset, then the sample from which the dataset was
obtained is classified as belonging to the reference dataset
class.
[0121] The predictive ability of a model can be evaluated according
to its ability to provide a quality metric, e.g. AUROC (area under
the ROC curve) or accuracy, of a particular value, or range of
values. Area under the curve measures are useful for comparing the
accuracy of a classifier across the complete data range.
Classifiers with a greater AUC have a greater capacity to classify
unknowns correctly between two groups of interest. In some
embodiments, a desired quality threshold is a predictive model that
will classify a sample with an accuracy of at least about 0.5, at
least about 0.55, at least about 0.6, at least about 0.7, at least
about 0.75, at least about 0.8, at least about 0.85, at least about
0.9, at least about 0.95, or higher. As an alternative measure, a
desired quality threshold can refer to a predictive model that will
classify a sample with an AUC of at least about 0.7, at least about
0.75, at least about 0.8, at least about 0.85, at least about 0.9,
or higher.
[0122] As is known in the art, the relative sensitivity and
specificity of a predictive model can be adjusted to favor either
the selectivity metric or the sensitivity metric, where the two
metrics have an inverse relationship. The limits in a model as
described above can be adjusted to provide a selected sensitivity
or specificity level, depending on the particular requirements of
the test being performed. One or both of sensitivity and
specificity can be at least about 0.7, at least about 0.75, at
least about 0.8, at least about 0.85, at least about 0.9, or
higher.
[0123] The raw data can be initially analyzed by measuring the
values for each biomarker, usually in triplicate or in multiple
triplicates. The data can be manipulated, for example, raw data can
be transformed using standard curves, and the average of triplicate
measurements used to calculate the average and standard deviation
for each patient. These values can be transformed before being used
in the models, e.g. log-transformed, Box-Cox transformed (Box and
Cox, Royal Stat. Soc., Series B, 26:211-246(1964). The data are
then input into a predictive model, which will classify the sample
according to the state. The resulting information can be
communicated to a patient or health care provider.
[0124] To generate a predictive model for preterm birth, a robust
data set, comprising known control samples and samples
corresponding to the preterm birth classification of interest is
used in a training set. A sample size can be selected using
generally accepted criteria. As discussed above, different
statistical methods can be used to obtain a highly accurate
predictive model. Examples of such analysis are provided in Example
2.
[0125] In one embodiment, hierarchical clustering is performed in
the derivation of a predictive model, where the Pearson correlation
is employed as the clustering metric. One approach is to consider a
preterm birth dataset as a "learning sample" in a problem of
"supervised learning." CART is a standard in applications to
medicine (Singer, Recursive Partitioning in the Health Sciences,
Springer(1999)) and can be modified by transforming any qualitative
features to quantitative features; sorting them by attained
significance levels, evaluated by sample reuse methods for
Hotelling's T.sup.2 statistic; and suitable application of the
lasso method. Problems in prediction are turned into problems in
regression without losing sight of prediction, indeed by making
suitable use of the Gini criterion for classification in evaluating
the quality of regressions.
[0126] This approach led to what is termed FlexTree (Huang, Proc.
Nat. Acad. Sci. U.S.A 101:10529-10534(2004)). FlexTree performs
very well in simulations and when applied to multiple forms of data
and is useful for practicing the claimed methods. Software
automating FlexTree has been developed. Alternatively, LARTree or
LART can be used (Turnbull (2005) Classification Trees with Subset
Analysis Selection by the Lasso, Stanford University). The name
reflects binary trees, as in CART and FlexTree; the lasso, as has
been noted; and the implementation of the lasso through what is
termed LARS by Efron et al. (2004) Annals of Statistics 32:407-451
(2004). See, also, Huang et al., Proc. Natl. Acad. Sci. USA.
101(29):10529-34 (2004). Other methods of analysis that can be used
include logic regression. One method of logic regression Ruczinski,
Journal of Computational and Graphical Statistics 12:475-512
(2003). Logic regression resembles CART in that its classifier can
be displayed as a binary tree. It is different in that each node
has Boolean statements about features that are more general than
the simple "and" statements produced by CART.
[0127] Another approach is that of nearest shrunken centroids
(Tibshirani, Proc. Natl. Acad. Sci. U.S.A 99:6567-72(2002)). The
technology is k-means-like, but has the advantage that by shrinking
cluster centers, one automatically selects features, as is the case
in the lasso, to focus attention on small numbers of those that are
informative. The approach is available as PAM software and is
widely used. Two further sets of algorithms that can be used are
random forests (Breiman, Machine Learning 45:5-32 (2001)) and MART
(Hastie, The Elements of Statistical Learning, Springer (2001)).
These two methods are known in the art as "committee methods," that
involve predictors that "vote" on outcome.
[0128] To provide significance ordering, the false discovery rate
(FDR) can be determined. First, a set of null distributions of
dissimilarity values is generated. In one embodiment, the values of
observed profiles are permuted to create a sequence of
distributions of correlation coefficients obtained out of chance,
thereby creating an appropriate set of null distributions of
correlation coefficients (Tusher et al., Proc. Natl. Acad. Sci.
U.S.A 98, 5116-21 (2001)). The set of null distribution is obtained
by: permuting the values of each profile for all available
profiles; calculating the pair-wise correlation coefficients for
all profile; calculating the probability density function of the
correlation coefficients for this permutation; and repeating the
procedure for N times, where N is a large number, usually 300.
Using the N distributions, one calculates an appropriate measure
(mean, median, etc.) of the count of correlation coefficient values
that their values exceed the value (of similarity) that is obtained
from the distribution of experimentally observed similarity values
at given significance level.
[0129] The FDR is the ratio of the number of the expected falsely
significant correlations (estimated from the correlations greater
than this selected Pearson correlation in the set of randomized
data) to the number of correlations greater than this selected
Pearson correlation in the empirical data (significant
correlations). This cut-off correlation value can be applied to the
correlations between experimental profiles. Using the
aforementioned distribution, a level of confidence is chosen for
significance. This is used to determine the lowest value of the
correlation coefficient that exceeds the result that would have
obtained by chance. Using this method, one obtains thresholds for
positive correlation, negative correlation or both. Using this
threshold(s), the user can filter the observed values of the pair
wise correlation coefficients and eliminate those that do not
exceed the threshold(s). Furthermore, an estimate of the false
positive rate can be obtained for a given threshold. For each of
the individual "random correlation" distributions, one can find how
many observations fall outside the threshold range. This procedure
provides a sequence of counts. The mean and the standard deviation
of the sequence provide the average number of potential false
positives and its standard deviation.
[0130] In an alternative analytical approach, variables chosen in
the cross-sectional analysis are separately employed as predictors
in a time-to-event analysis (survival analysis), where the event is
the occurrence of preterm birth, and subjects with no event are
considered censored at the time of giving birth. Given the specific
pregnancy outcome (preterm birth event or no event), the random
lengths of time each patient will be observed, and selection of
proteomic and other features, a parametric approach to analyzing
survival can be better than the widely applied semi-parametric Cox
model. A Weibull parametric fit of survival permits the hazard rate
to be monotonically increasing, decreasing, or constant, and also
has a proportional hazards representation (as does the Cox model)
and an accelerated failure-time representation. All the standard
tools available in obtaining approximate maximum likelihood
estimators of regression coefficients and corresponding functions
are available with this model.
[0131] In addition the Cox models can be used, especially since
reductions of numbers of covariates to manageable size with the
lasso will significantly simplify the analysis, allowing the
possibility of a nonparametric or semi-parametric approach to
prediction of time to preterm birth. These statistical tools are
known in the art and applicable to all manner of proteomic data. A
set of biomarker, clinical and genetic data that can be easily
determined, and that is highly informative regarding the
probability for preterm birth and predicted time to a preterm birth
event in said pregnant female is provided. Also, algorithms provide
information regarding the probability for preterm birth in the
pregnant female.
[0132] Accordingly, one skilled in the art understands that the
probability for preterm birth according to the invention can be
determined using either a quantitative or a categorical variable.
For example, in practicing the methods of the invention the
measurable feature of each of N biomarkers can be subjected to
categorical data analysis to determine the probability for preterm
birth as a binary categorical outcome. Alternatively, the methods
of the invention may analyze the measurable feature of each of N
biomarkers by initially calculating quantitative variables, in
particular, predicted gestational age at birth. The predicted
gestational age at birth can subsequently be used as a basis to
predict risk of preterm birth. By initially using a quantitative
variable and subsequently converting the quantitative variable into
a categorical variable the methods of the invention take into
account the continuum of measurements detected for the measurable
features. For example, by predicting the gestational age at birth
rather than making a binary prediction of preterm birth versus term
birth, it is possible to tailor the treatment for the pregnant
female. For example, an earlier predicted gestational age at birth
will result in more intensive prenatal intervention, i.e.
monitoring and treatment, than a predicted gestational age that
approaches full term.
[0133] Among women with a predicted GAB of j days plus or minus k
days, p(PTB) can estimated as the proportion of women in the PAPR
clinical trial (see Example 1) with a predicted GAB of j days plus
or minus k days who actually deliver before 37 weeks gestational
age. More generally, for women with a predicted GAB of j days plus
or minus k days, the probability that the actual gestational age at
birth will be less than a specified gestational age, p(actual GAB
<specified GAB), was estimated as the proportion of women in the
PAPR clinical trial with a predicted GAB of j days plus or minus k
days who actually deliver before the specified gestational age.
[0134] In the development of a predictive model, it can be
desirable to select a subset of markers, i.e. at least 3, at least
4, at least 5, at least 6, up to the complete set of markers.
Usually a subset of markers will be chosen that provides for the
needs of the quantitative sample analysis, e.g. availability of
reagents, convenience of quantitation, etc., while maintaining a
highly accurate predictive model. The selection of a number of
informative markers for building classification models requires the
definition of a performance metric and a user-defined threshold for
producing a model with useful predictive ability based on this
metric. For example, the performance metric can be the AUC, the
sensitivity and/or specificity of the prediction as well as the
overall accuracy of the prediction model.
[0135] As will be understood by those skilled in the art, an
analytic classification process can use any one of a variety of
statistical analytic methods to manipulate the quantitative data
and provide for classification of the sample. Examples of useful
methods include, without limitation, linear discriminant analysis,
recursive feature elimination, a prediction analysis of microarray,
a logistic regression, a CART algorithm, a FlexTree algorithm, a
LART algorithm, a random forest algorithm, a MART algorithm, and
machine learning algorithms.
[0136] As described in Example 2, various methods are used in a
training model. The selection of a subset of markers can be for a
forward selection or a backward selection of a marker subset. The
number of markers can be selected that will optimize the
performance of a model without the use of all the markers. One way
to define the optimum number of terms is to choose the number of
terms that produce a model with desired predictive ability (e.g. an
AUC>0.75, or equivalent measures of sensitivity/specificity)
that lies no more than one standard error from the maximum value
obtained for this metric using any combination and number of terms
used for the given algorithm.
TABLE-US-00001 TABLE 1 Transitions with p-values less than 0.05 in
univariate Cox Proportional Hazards analyses to predict Gestational
Age at Birth p-value Cox uni- Transition Protein variate
ITLPDFTGDLR_624.34_920.4 LBP_HUMAN 0.006 ELLESYIDGR_597.8_710.3
THRB_HUMAN 0.006 TDAPDLPEENQAR_728.34_613.3 CO5_HUMAN 0.007
AFTECCVVASQLR_770.87_574.3 CO5_HUMAN 0.009 SFRPFVPR_335.86_272.2
LBP_HUMAN 0.011 ITLPDFTGDLR_624.34_288.2 LBP_HUMAN 0.012
SFRPFVPR_335.86_635.3 LBP_HUMAN 0.015 ELLESYIDGR_597.8_839.4
THRB_HUMAN 0.018 LEQGENVFLQATDK_796.4_822.4 C1QB_HUMAN 0.019
ETAASLLQAGYK_626.33_679.4 THRB_HUMAN 0.021 VTGWGNLK_437.74_617.3
THRB_HUMAN 0.021 EAQLPVIENK_570.82_699.4 PLMN_HUMAN 0.023
EAQLPVIENK_570.82_329.1 PLMN_HUMAN 0.023 FLQEQGHR_338.84_497.3
CO8G_HUMAN 0.025 IRPFFPQQ_516.79_661.4 FIBB_HUMAN 0.028
ETAASLLQAGYK_626.33_879.5 THRB_HUMAN 0.029
AFTECCVVASQLR_770.87_673.4 CO5_HUMAN 0.030 TLLPVSKPEIR_418.26_288.2
CO5_HUMAN 0.030 LSSPAVITDK_515.79_743.4 PLMN_HUMAN 0.033
YEVQGEVFTKPQLWP_910.96_392.2 CRP_HUMAN 0.036
LQGTLPVEAR_542.31_571.3 CO5_HUMAN 0.036 VRPQQLVK_484.31_609.3
ITIH4_HUMAN 0.036 IEEIAAK_387.22_531.3 CO5_HUMAN 0.041
TLLPVSKPEIR_418.26_514.3 CO5_HUMAN 0.042
VQEAHLTEDQIFYFPK_655.66_701.4 CO8G_HUMAN 0.047
ISLLLIESWLEPVR_834.49_371.2 CSH_HUMAN 0.048
ALQDQLVLVAAK_634.88_289.2 ANGT_HUMAN 0.048 YEFLNGR_449.72_293.1
PLMN_HUMAN 0.049
TABLE-US-00002 TABLE 2 Transitions selected by the Cox stepwise AIC
analysis Transition coef exp(coef) se(coef) z Pr(>|z|)
Collection.Window.GA.in.Days 1.28E-01 1.14E+00 2.44E-02 5.26
1.40E-07 ITLPDFTGDLR_624.34_920.4 2.02E+00 7.52E+00 1.14E+00 1.77
0.07667 TPSAAYLWVGTGASEAEK_919.45_849.4 2.85E+01 2.44E+12 3.06E+00
9.31 <2e-16 TATSEYQTFFNPR_781.37_386.2 5.14E+00 1.70E+02
6.26E-01 8.21 2.20E-16 TASDFITK_441.73_781.4 -1.25E+00 2.86E-01
1.58E+00 -0.79 0.42856 IITGLLEFEVYLEYLQNR_738.4_530.3 1.30E+01
4.49E+05 1.45E+00 9 <2e-16 IIGGSDADIK_494.77_762.4 -6.43E+01
1.16E-28 6.64E+00 -9.68 <2e-16 YTTEIIK_434.25_603.4 6.96E+01
1.75E+30 7.06E+00 9.86 <2e-16 EDTPNSVWEPAK_686.82_315.2 7.91E+00
2.73E+03 2.66E+00 2.98 0.00293 LYYGDDEK_501.72_726.3 8.74E+00
6.23E+03 1.57E+00 5.57 2.50E-08 VRPQQLVK_484.31_609.3 4.64E+01
1.36E+20 3.97E+00 11.66 <2e-16 GGEIEGFR_432.71_379.2 -3.33E+00
3.57E-02 2.19E+00 -1.52 0.12792 DGSPDVTTADIGANTPDATK_973.45_844.4
-1.52E+01 2.51E-07 1.41E+00 -10.8 <2e-16
VQEAHLTEDQIFYFPK_655.66_391.2 -2.02E+01 1.77E-09 2.45E+00 -8.22
2.20E-16 VEIDTK_352.7_476.3 7.06E+00 1.17E+03 1.45E+00 4.86
1.20E-06 AVLTIDEK_444.76_605.3 7.85E+00 2.56E+03 9.46E-01 8.29
<2e-16 FSVVYAK_407.23_579.4 -2.44E+01 2.42E-11 3.08E+00 -7.93
2.20E-15 YYLQGAK_421.72_516.3 -1.82E+01 1.22E-08 2.45E+00 -7.44
1.00E-13 EENFYVDETTVVK_786.88_259.1 -1.90E+01 5.36E-09 2.71E+00
-7.03 2.00E-12 YGFYTHVFR_397.2_421.3 1.90E+01 1.71E+08 2.73E+00
6.93 4.20E-12 HTLNQIDEVK_598.82_951.5 1.03E+01 3.04E+04 2.11E+00
4.89 9.90E-07 AFIQLWAFDAVK_704.89_836.4 1.08E+01 4.72E+04 2.59E+00
4.16 3.20E-05 SGFSFGFK_438.72_585.3 1.35E+01 7.32E+05 2.56E+00 5.27
1.40E-07 GWVTDGFSSLK_598.8_854.4 -3.12E+00 4.42E-02 9.16E-01 -3.4
0.00066 ITENDIQIALDDAK_779.9_632.3 1.91E+00 6.78E+00 1.36E+00 1.4
0.16036
TABLE-US-00003 TABLE 3 Transitions selected by Cox lasso model
Transition coef exp(coef) se(coef) z Pr(>|z|)
Collection.Window.GA.in.Days 0.0233 1.02357 0.00928 2.51 0.012
AFTECCVVASQLR_770.87_574.3 1.07568 2.93198 0.84554 1.27 0.203
ELLESYIDGR_597.8_710.3 1.3847 3.99365 0.70784 1.96 0.05
ITLPDFTGDLR_624.34_920.4 0.814 2.25691 0.40652 2 0.045
TABLE-US-00004 TABLE 4 Area under the ROC (AUROC) curve for
individual analytes to discriminate pre-term birth subjects from
non-pre-term birth subjects. The 77 transitions with the highest
AUROC area are shown. Transition AUROC ELLESYIDGR_597.8_710.3 0.71
AFTECCVVASQLR_770.87_574.3 0.70 ITLPDFTGDLR_624.34_920.4 0.70
IRPFFPQQ_516.79_661.4 0.68 TDAPDLPEENQAR_728.34_613.3 0.67
ITLPDFTGDLR_624.34_288.2 0.67 ELLESYIDGR_597.8_839.4 0.67
SFRPFVPR_335.86_635.3 0.67 ETAASLLQAGYK_626.33_879.5 0.67
TLLPVSKPEIR_418.26_288.2 0.66 ETAASLLQAGYK_626.33_679.4 0.66
SFRPFVPR_335.86_272.2 0.66 LQGTLPVEAR_542.31_571.3 0.66
VEPLYELVTATDFAYSSTVR_754.38_712.4 0.66
DPDQTDGLGLSYLSSHIANVER_796.39_328.1 0.66 VTGWGNLK_437.74_617.3 0.65
ALQDQLVLVAAK_634.88_289.2 0.65 EAQLPVIENK_570.82_329.1 0.65
VRPQQLVK_484.31_609.3 0.65 AFTECCVVASQLR_770.87_673.4 0.65
YEFLNGR_449.72_293.1 0.65 VGEYSLYIGR_578.8_871.5 0.64
EAQLPVIENK_570.82_699.4 0.64 TLLPVSKPEIR_418.26_514.3 0.64
IEEIAAK_387.22_531.3 0.64 LEQGENVFLQATDK_796.4_822.4 0.64
LQGTLPVEAR_542.31_842.5 0.64 FLQEQGHR_338.84_497.3 0.63
ISLLLIESWLEPVR_834.49_371.2 0.63 IITGLLEFEVYLEYLQNR_738.4_530.3
0.63 LSSPAVITDK_515.79_743.4 0.63 VRPQQLVK_484.31_722.4 0.63
SLPVSDSVLSGFEQR_810.92_723.3 0.63 VQEAHLTEDQIFYFPK_655.66_701.4
0.63 NADYSYSVWK_616.78_333.2 0.63 DAQYAPGYDK_564.25_813.4 0.62
FQLPGQK_409.23_276.1 0.62 TASDFITK_441.73_781.4 0.62
YGLVTYATYPK_638.33_334.2 0.62 GSFALSFPVESDVAPIAR_931.99_363.2 0.62
TLLIANETLR_572.34_703.4 0.62 VILGAHQEVNLEPHVQEIEVSR_832.78_860.4
0.62 TATSEYQTFFNPR_781.37_386.2 0.62 YEVQGEVFTKPQLWP_910.96_392.2
0.62 DISEVVTPR_508.27_472.3 0.62 GSFALSFPVESDVAPIAR_931.99_456.3
0.62 YGFYTHVFR_397.2_421.3 0.62 TLEAQLTPR_514.79_685.4 0.62
YGFYTHVFR_397.2_659.4 0.62 AVGYLITGYQR_620.84_737.4 0.61
DPDQTDGLGLSYLSSHIANVER_796.39_456.2 0.61
FNAVLTNPQGDYDTSTGK_964.46_262.1 0.61 SPEQQETVLDGNLIIR_906.48_685.4
0.61 ALNHLPLEYNSALYSR_620.99_538.3 0.61 GGEIEGFR_432.71_508.3 0.61
GIVEECCFR_585.26_900.3 0.61 DAQYAPGYDK_564.25_315.1 0.61
FAFNLYR_465.75_712.4 0.61 YTTEIIK_434.25_603.4 0.61
AVLTIDEK_444.76_605.3 0.61 AITPPHPASQANIIFDITEGNLR_825.77_459.3
0.60 EPGLCTWQSLR_673.83_790.4 0.60 AVYEAVLR_460.76_587.4 0.60
ALQDQLVLVAAK_634.88_956.6 0.60 AWVAWR_394.71_531.3 0.60
TNLESILSYPK_632.84_807.5 0.60 HLSLLTTLSNR_418.91_376.2 0.60
FTFTLHLETPKPSISSSNLNPR_829.44_787.4 0.60 AVGYLITGYQR_620.84_523.3
0.60 FQLPGQK_409.23_429.2 0.60 YGLVTYATYPK_638.33_843.4 0.60
TELRPGETLNVNFLLR_624.68_662.4 0.60 LSSPAVITDK_515.79_830.5 0.60
TATSEYQTFFNPR_781.37_272.2 0.60 LPTAVVPLR_483.31_385.3 0.60
APLTKPLK_289.86_260.2 0.60
TABLE-US-00005 TABLE 5 AUROCs for random forest, boosting, lasso,
and logistic regression models for a specific number of transitions
permitted in the model, as estimated by 100 rounds of bootstrap
resampling. Number of transitions rf boosting logit lasso 1 0.59
0.67 0.64 0.69 2 0.66 0.70 0.63 0.68 3 0.69 0.70 0.58 0.71 4 0.68
0.72 0.58 0.71 5 0.73 0.71 0.58 0.68 6 0.72 0.72 0.56 0.68 7 0.74
0.70 0.60 0.67 8 0.73 0.72 0.62 0.67 9 0.72 0.72 0.60 0.67 10 0.74
0.71 0.62 0.66 11 0.73 0.69 0.58 0.67 12 0.73 0.69 0.59 0.66 13
0.74 0.71 0.57 0.66 14 0.73 0.70 0.57 0.65 15 0.72 0.70 0.55
0.64
TABLE-US-00006 TABLE 6 Top 15 transitions selected by each
multivariate method, ranked by importance for that method. rf
boosting lasso logit 1 ELLESYIDGR_597.8_710.3 AFTECCVVASQL
AFTECCVVASQ ALQDQLVLVA R_770.87_574.3 LR_770.87_574.3
AK_634.88_289.2 2 TATSEYQTFF DPDQTDGLGLSY ISLLLIESWLEP
AVLTIDEK_444.76_605.3 NPR_781.37_386.2 LSSHIANVER_796.39_328.1
VR_834.49_371.2 3 ITLPDFTGDLR_624.34_920.4 ELLESYIDGR_597.8_710.3
LPTAVVPLR_483.31_385.3 Collection.Window.G A.in.Days 4 AFTECCVVAS
TATSEYQTFFNPR_781.37_386.2 ALQDQLVLVA AHYDLR_387.7_566.3
QLR_770.87_574.3 AK_634.88_289.2 5 VEPLYELVTA
ITLPDFTGDLR_624.34_920.4 ETAASLLQAG AEAQAQYSAAVA
TDFAYSSTVR_754.38_712.4 YK_626.33_679.4 K_654.33_908.5 6
GSFALSFPVES GGEIEGFR_432.71_379.2 IITGLLEFEVYLEYL AEAQAQYSAAVA
DVAPIAR_931.99_363.2 QNR_738.4_530.3 K_654.33_709.4 7
VGEYSLYIGR_578.8_871.5 ALQDQLVLVAAK_634.88_289.2 ADSQAQLLLSTVV
ADSQAQLLLSTVV GVFTAPGLHLK_822.46_983.6 GVFTAPGLHLK_822.46_983.6 8
SFRPFVPR_335.86_635.3 VGEYSLYIGR_578.8_871.5 SLPVSDSVLSGFEQ
AITPPHPASQANIIF R_810.92_723.3 DITEGNLR_825.77_459.3 9 ALQDQLVLVA
VEPLYELVTATD SFRPFVPR_335.86_272.2 ADSQAQLLLSTVV AK_634.88_289.2
FAYSSTVR_754.38_712.4 GVFTAPGLHLK_822.46_664.4 10 EDTPNSVWEP
SPEQQETVLDGN IIGGSDADIK_494.77_260.2 AYSDLSR_406.2_375.2
AK_686.82_315.2 LIIR_906.48_685.4 11 YGFYTHVFR_397.2_421.3
YEFLNGR_449.72_293.1 NADYSYSVWK_616.78_333.2 DALSSVQESQVAQ
QAR_572.96_672.4 12 DPDQTDGLGL LEQGENVFLQAT GSFALSFPVESDVA
ANRPFLVFIR_411.58_435.3 SYLSSHIANVE DK_796.4_822.4
PIAR_931.99_456.3 R_796.39_328.1 13 LEQGENVFLQ
LQGTLPVEAR_542.31_571.3 LSSPAVITDK_515.79_743.4 DALSSVQESQVAQ
ATDK_796.4_822.4 QAR_572.96_502.3 14 LQGTLPVEAR_542.31_571.3
ISLLLIESWLEP ELPEHTVK_476.76_347.2 ALEQDLPVNIK_620.35_570.4
VR_834.49_371.2 15 SFRPFVPR_335.86_272.2 TASDFITK_441.73_781.4
EAQLPVIENK_570.82_699.4 AVLTIDEK_444.76_718.4
[0137] In yet another aspect, the invention provides kits for
determining probability of preterm birth, wherein the kits can be
used to detect N of the isolated biomarkers listed in Tables 1
through 63. For example, the kits can be used to detect one or
more, two or more, or three of the isolated biomarkers selected
from the group consisting of AFTECCVVASQLR, ELLESYIDGR, and
ITLPDFTGDLR. For example, the kits can be used to detect one or
more, two or more, or three of the isolated biomarkers selected
from the group consisting of FLNWIK, FGFGGSTDSGPIR, LLELTGPK,
VEHSDLSFSK, IEGNLIFDPNNYLPK, ALVLELAK, TQILEWAAER,
DVLLLVHNLPQNLPGYFWYK, SEPRPGVLLR, ITQDAQLK, ALDLSLK, WWGGQPLWITATK,
and LSETNR.
[0138] In another aspect, the kits can be used to detect one or
more, two or more, three or more, four or more, five or more, six
or more, seven or more, or eight of the isolated biomarkers
selected from the group consisting of lipopolysaccharide-binding
protein (LBP), prothrombin (THRB), complement component C5 (C5 or
CO5), plasminogen (PLMN), and complement component C8 gamma chain
(C8G or CO8G).
[0139] In another aspect, the kits can be used to detect one or
more, two or more, three or more, four or more, five or more, six
or more, seven or more, or eight of the isolated biomarkers
selected from the group consisting of Alpha-1B-glycoprotein (A1BG),
Disintegrin and metalloproteinase domain-containing protein 12
(ADA12), Apolipoprotein B-100 (APOB), Beta-2-microglobulin (B2MG),
CCAAT/enhancer-binding protein alpha/beta (HP8 Peptide),
Corticosteroid-binding globulin (CBG), Complement component C6,
Endoglin (EGLN), Ectonucleotide pyrophosphatase/phosphodiesterase
family member 2 (ENPP2), Coagulation factor VII (FA7),
Hyaluronan-binding protein 2 (HABP2), Pregnancy-specific
beta-1-glycoprotein 9 (PSG9), Inhibin beta E chain (INHBE).
[0140] The kit can include one or more agents for detection of
biomarkers, a container for holding a biological sample isolated
from a pregnant female; and printed instructions for reacting
agents with the biological sample or a portion of the biological
sample to detect the presence or amount of the isolated biomarkers
in the biological sample. The agents can be packaged in separate
containers. The kit can further comprise one or more control
reference samples and reagents for performing an immunoassay.
[0141] In one embodiment, the kit comprises agents for measuring
the levels of at least N of the isolated biomarkers listed in
Tables 1 through 63. The kit can include antibodies that
specifically bind to these biomarkers, for example, the kit can
contain at least one of an antibody that specifically binds to
lipopolysaccharide-binding protein (LBP), an antibody that
specifically binds to prothrombin (THRB), an antibody that
specifically binds to complement component C5 (C5 or CO5), an
antibody that specifically binds to plasminogen (PLMN), and an
antibody that specifically binds to complement component C8 gamma
chain (C8G or CO8G).
[0142] In one embodiment, the kit comprises agents for measuring
the levels of at least N of the isolated biomarkers listed in
Tables 1 through 63. The kit can include antibodies that
specifically bind to these biomarkers, for example, the kit can
contain at least one of an antibody that specifically binds to
Alpha-1B-glycoprotein (A1BG), Disintegrin and metalloproteinase
domain-containing protein 12 (ADA12), Apolipoprotein B-100 (APOB),
Beta-2-microglobulin (B2MG), CCAAT/enhancer-binding protein
alpha/beta (HP8 Peptide), Corticosteroid-binding globulin (CBG),
Complement component C6, Endoglin (EGLN), Ectonucleotide
pyrophosphatase/phosphodiesterase family member 2 (ENPP2),
Coagulation factor VII (FA7), Hyaluronan-binding protein 2 (HABP2),
Pregnancy-specific beta-1-glycoprotein 9 (PSG9), Inhibin beta E
chain (INHBE).
[0143] The kit can comprise one or more containers for compositions
contained in the kit. Compositions can be in liquid form or can be
lyophilized. Suitable containers for the compositions include, for
example, bottles, vials, syringes, and test tubes. Containers can
be formed from a variety of materials, including glass or plastic.
The kit can also comprise a package insert containing written
instructions for methods of determining probability of preterm
birth.
[0144] From the foregoing description, it will be apparent that
variations and modifications can be made to the invention described
herein to adopt it to various usages and conditions. Such
embodiments are also within the scope of the following claims.
[0145] The recitation of a listing of elements in any definition of
a variable herein includes definitions of that variable as any
single element or combination (or subcombination) of listed
elements. The recitation of an embodiment herein includes that
embodiment as any single embodiment or in combination with any
other embodiments or portions thereof.
[0146] All patents and publications mentioned in this specification
are herein incorporated by reference to the same extent as if each
independent patent and publication was specifically and
individually indicated to be incorporated by reference.
[0147] The following examples are provided by way of illustration,
not limitation.
EXAMPLES
Example 1
Development of Sample Set for Discovery and Validation of
Biomarkers for Preterm Birth
[0148] A standard protocol was developed governing conduct of the
Proteomic Assessment of Preterm Risk (PAPR) clinical study. This
protocol also specified that the samples and clinical information
could be used to study other pregnancy complications for some of
the subjects. Specimens were obtained from women at 11 Internal
Review Board (IRB) approved sites across the United States. After
providing informed consent, serum and plasma samples were obtained,
as well as pertinent information regarding the patient's
demographic characteristics, past medical and pregnancy history,
current pregnancy history and concurrent medications. Following
delivery, data were collected relating to maternal and infant
conditions and complications. Serum and plasma samples were
processed according to a protocol that requires standardized
refrigerated centrifugation, aliquoting of the samples into 0.5 ml
2-D bar-coded cryovials and subsequent freezing at -80.degree.
C.
[0149] Following delivery, preterm birth cases were individually
reviewed to determine their status as either a spontaneous preterm
birth or a medically indicated preterm birth. Only spontaneous
preterm birth cases were used for this analysis. For discovery of
biomarkers of preterm birth, 80 samples were analyzed in two
gestational age groups: a) a late window composed of samples from
23-28 weeks of gestation which included 13 cases, 13 term controls
matched within one week of sample collection and 14 term random
controls, and, b) an early window composed of samples from 17-22
weeks of gestation included 15 cases, 15 term controls matched
within one week of sample collection and 10 random term
controls.
[0150] The samples were subsequently depleted of high abundance
proteins using the Human 14 Multiple Affinity Removal System (MARS
14), which removes 14 of the most abundant proteins that are
treated as uninformative with regard to the identification for
disease-relevant changes in the serum proteome. To this end, equal
volumes of each clinical or a pooled human serum sample (HGS)
sample were diluted with column buffer and filtered to remove
precipitates. Filtered samples were depleted using a MARS-14 column
(4.6.times.100 mm, Cat. #5188-6558, Agilent Technologies). Samples
were chilled to 4.degree. C. in the autosampler, the depletion
column was run at room temperature, and collected fractions were
kept at 4.degree. C. until further analysis. The unbound fractions
were collected for further analysis.
[0151] A second aliquot of each clinical serum sample and of each
HGS was diluted into ammonium bicarbonate buffer and depleted of
the 14 high and approximately 60 additional moderately abundant
proteins using an IgY14-SuperMix (Sigma) hand-packed column,
comprised of 10 mL of bulk material (50% slurry, Sigma). Shi et
al., Methods, 56(2):246-53 (2012). Samples were chilled to
4.degree. C. in the autosampler, the depletion column was run at
room temperature, and collected fractions were kept at 4.degree. C.
until further analysis. The unbound fractions were collected for
further analysis.
[0152] Depleted serum samples were denatured with trifluorethanol,
reduced with dithiotreitol, alkylated using iodoacetamide, and then
digested with trypsin at a 1:10 trypsin: protein ratio. Following
trypsin digestion, samples were desalted on a C18 column, and the
eluate lyophilized to dryness. The desalted samples were
resolubilized in a reconstitution solution containing five internal
standard peptides.
[0153] Depleted and trypsin digested samples were analyzed using a
scheduled Multiple Reaction Monitoring method (sMRM). The peptides
were separated on a 150 mm.times.0.32 mm Bio-Basic C18 column
(ThermoFisher) at a flow rate of 5 .mu.l/min using a Waters Nano
Acquity UPLC and eluted using an acetonitrile gradient into a AB
SCIEX QTRAP 5500 with a Turbo V source (AB SCIEX, Framingham,
Mass.). The sMRM assay measured 1708 transitions that correspond to
854 peptides and 236 proteins. Chromatographic peaks were
integrated using Rosetta Elucidator software (Ceiba Solutions).
[0154] Transitions were excluded from analysis, if their intensity
area counts were less than 10000 and if they were missing in more
than three samples per batch. Intensity area counts were log
transformed and Mass Spectrometry run order trends and depletion
batch effects were minimized using a regression analysis.
Example 2
Analysis I of Transitions to Identify Preterm Birth Biomarkers
[0155] The objective of these analyses was to examine the data
collected in Example 1 to identify transitions and proteins that
predict preterm birth. The specific analyses employed were (i) Cox
time-to-event analyses and (ii) models with preterm birth as a
binary categorical dependent variable. The dependent variable for
all the Cox analyses was Gestational Age of time to event (where
event is preterm birth). For the purpose of the Cox analyses,
preterm birth subjects have the event on the day of birth. Term
subjects are censored on the day of birth. Gestational age on the
day of specimen collection is a covariate in all Cox analyses.
[0156] The assay data were previously adjusted for run order and
depletion batch, and log transformed. Values for gestational age at
time of sample collection were adjusted as follows. Transition
values were regressed on gestational age at time of sample
collection using only controls (non-pre-term subjects). The
residuals from the regression were designated as adjusted values.
The adjusted values were used in the models with pre-term birth as
a binary categorical dependent variable. Unadjusted values were
used in the Cox analyses.
[0157] Univariate Cox Proportional Hazards Analyses
[0158] Univariate Cox Proportional Hazards analyses was performed
to predict Gestational Age at Birth, including Gestational age on
the day of specimen collection as a covariate. Table 1 shows the
transitions with p-values less than 0.05. Five proteins have
multiple transitions among those with p-value less than 0.05:
lipopolysaccharide-binding protein (LBP), prothrombin (THRB),
complement component C5 (C5 or CO5), plasminogen (PLMN), and
complement component C8 gamma chain (C8G or CO8G).
[0159] Multivariate Cox Proportional Hazards Analyses: Stepwise AIC
Selection
[0160] Cox Proportional Hazards analyses was performed to predict
Gestational Age at Birth, including Gestational age on the day of
specimen collection as a covariate, using stepwise and lasso models
for variable selection. These analyses include a total of n=80
subjects, with number of PTB events=28. The stepwise variable
selection analysis used the Akaike Information Criterion (AIC) as
the stopping criterion. Table 2 shows the transitions selected by
the stepwise AIC analysis. The coefficient of determination
(R.sup.2) for the stepwise AIC model is 0.86 (not corrected for
multiple comparisons).
[0161] Multivariate Cox Proportional Hazards Analyses: Lasso
Selection
[0162] Lasso variable selection was used as the second method of
multivariate Cox Proportional Hazards analyses to predict
Gestational Age at Birth, including Gestational age on the day of
specimen collection as a covariate. This analysis uses a lambda
penalty for lasso estimated by cross validation. Table 3 shows the
results. The lasso variable selection method is considerably more
stringent than the stepwise AIC, and selects only 3 transitions for
the final model, representing 3 different proteins. These 3
proteins give the top 4 transitions from the univariate analysis; 2
of the top 4 univariate are from the same protein, and hence are
not both selected by the lasso method. Lasso tends to select a
relatively small number of variables with low mutual correlation.
The coefficient of determination (R.sup.2) for the lasso model is
0.21 (not corrected for multiple comparisons).
[0163] Univariate AUROC Analysis of Preterm Birth as a Binary
Categorical Dependent Variable
[0164] Univariate analyses was performed to discriminate pre-term
subjects from non-pre-term subjects (pre-term as a binary
categorical variable) as estimated by area under the receiver
operating characteristic (AUROC) curve. These analyses use
transition values adjusted for gestational age at time of sample
collection, as described above. Table 4 shows the AUROC curve for
the 77 transitions with the highest AUROC area of 0.6 or
greater.
[0165] Multivariate Analysis of Preterm Birth as a Binary
Categorical Dependent Variable
[0166] Multivariate analyses was performed to predict preterm birth
as a binary categorical dependent variable, using random forest,
boosting, lasso, and logistic regression models. Random forest and
boosting models grow many classification trees. The trees vote on
the assignment of each subject to one of the possible classes. The
forest chooses the class with the most votes over all the
trees.
[0167] For each of the four methods (random forest, boosting,
lasso, and logistic regression) each method was allowed to select
and rank its own best 15 transitions. We then built models with 1
to 15 transitions. Each method sequentially reduces the number of
nodes from 15 to 1 independently. A recursive option was used to
reduce the number of nodes at each step: To determine which node to
remove, the nodes were ranked at each step based on their
importance from a nested cross-validation procedure. The least
important node was eliminated. The importance measures for lasso
and logistic regression are z-values. For random forest and
boosting, the variable importance was calculated from permuting
out-of-bag data: for each tree, the classification error rate on
the out-of-bag portion of the data was recorded; the error rate was
then recalculated after permuting the values of each variable
(i.e., transition); if the transition was in fact important, there
would have been be a big difference between the two error rates;
the difference between the two error rates were then averaged over
all trees, and normalized by the standard deviation of the
differences. The AUCs for these models are shown in Table 5, as
estimated by 100 rounds of bootstrap resampling. Table 6 shows the
top 15 transitions selected by each multivariate method, ranked by
importance for that method. These multivariate analyses suggest
that models that combine 3 or more transitions give AUC greater
than 0.7, as estimated by bootstrap.
[0168] In multivariate models, random forest (rf), boosting, and
lasso models gave the best area under the AUROC curve. The
following transitions were selected by these models, as significant
in Cox univariate models, and/or having high univariate ROC'S:
TABLE-US-00007 AFTECCVVASQLR_770.87_574.3 ELLESYIDGR_597.8_710.3
ITLPDFTGDLR_624.34_920.4 TDAPDLPEENQAR_728.34_613.3
SFRPFVPR_335.86_635.3
[0169] In summary, univariate and multivariate Cox analyses was
performed using transitions to predict Gestational Age at Birth
(GAB), including Gestational age on the day of specimen collection
as a covariate. In the univariate Cox analysis, five proteins were
identified that have multiple transitions among those with p-value
less than 0.05: lipopolysaccharide-binding protein (LBP),
prothrombin (THRB), complement component C5 (C5 or CO5),
plasminogen (PLMN), and complement component C8 gamma chain (C8G or
CO8G).
[0170] In multivariate Cox analyses, stepwise AIC variable analysis
selects 24 transitions, while the lasso model selects 3
transitions, which include the 3 top proteins in the univariate
analysis. Univariate (AUROC) and multivariate (random forest,
boosting, lasso, and logistic regression) analyses were performed
to predict pre-term birth as a binary categorical variable.
Univariate analyses identified 63 analytes with AUROC of 0.6 or
greater. Multivariate analyses suggest that models that combine 3
or more transitions give AUC greater than 0.7, as estimated by
bootstrap.
Example 3
Study II to Identify and Confirm Preterm Birth Biomarkers
[0171] A further study was performed using essentially the same
methods described in the preceding Examples unless noted below. In
this study, 2 gestational aged matched controls were used for each
case of 28 cases and 56 matched controls, all from the early
gestational window only (17-22 weeks).
[0172] The samples were processed in 4 batches with each batch
composed of 7 cases, 14 matched controls and 3 HGS controls. Serum
samples were depleted of the 14 most abundant serum samples by
MARS14 as described in Example 1. Depleted serum was then reduced
with dithiothreitol, alkylated with iodacetamide, and then digested
with trypsin at a 1:20 trypsin to protein ratio overnight at
37.degree. C. Following trypsin digestion, the samples were
desalted on an Empore C18 96-well Solid Phase Extraction Plate (3M
Company) and lyophilized to dryness. The desalted samples were
resolubilized in a reconstitution solution containing five internal
standard peptides.
[0173] The LC-MS/MS analysis was performed with an Agilent
Poroshell 120 EC-C18 column (2.1.times.50 mm, 2.7 .mu.m) and eluted
with an acetonitrile gradient into a Agilent 6490 Triple Quadrapole
mass spectrometer.
[0174] Data analysis included the use of conditional logistic
regression where each matching triplet (case and 2 matched
controls) was a stratum. The p-value reported in the table
indicates whether there is a significant difference between cases
and matched controls.
TABLE-US-00008 TABLE 7 Results of Study II Transition Protein
Annotation p-value DFHINLFQVLPWLK CFAB_HUMAN Complement factor B
0.006729512 ITLPDFTGDLR LBP_HUMAN Lipopolysaccharide- 0.012907017
binding protein WWGGQPLWITATK ENPP2_HUMAN Ectonucleotide 0.013346
pyrophosphatase/ phosphodiesterase family member 2 TASDFITK
GELS_HUMAN Gelsolin 0.013841221 AGLLRPDYALLGHR PGRP2_HUMAN
N-acetylmuramoyl-L- 0.014241979 alanine amidase FLQEQGHR CO8G_HUMAN
Complement 0.014339596 component C8 gamma chain FLNWIK HABP2_HUMAN
Hyaluronan-binding 0.014790418 protein 2 EKPAGGIPVLGSLVNTVLK
BPIB1_HUMAN BPI fold-containing 0.019027746 family B member 1
ITGFLKPGK LBP_HUMAN Lipopolysaccharide- 0.019836986 binding protein
YGLVTYATYPK CFAB_HUMAN Complement factor B 0.019927774 SLLQPNK
CO8A_HUMAN Complement 0.020930939 component C8 alpha chain
DISEVVTPR CFAB_HUMAN Complement factor B 0.021738046
VQEAHLTEDQIFYFPK CO8G_HUMAN Complement 0.021924548 component C8
gamma chain SPELQAEAK APOA2_HUMAN Apolipoprotein A-II 0.025944285
TYLHTYESEI ENPP2_HUMAN Ectonucleotide 0.026150038 pyrophosphatase/
phosphodiesterase family member 2 DSPSVWAAVPGK PROF1_HUMAN
Profilin-1 0.026607371 HYINLITR NPY_HUMAN Pro-neuropeptide Y
0.027432804 SLPVSDSVLSGFEQR CO8G_HUMAN Complement 0.029647857
component C8 gamma chain IPGIFELGISSQSDR CO8B_HUMAN Complement
0.030430996 component C8 beta chain IQTHSTTYR F13B_HUMAN
Coagulation factor XIII 0.031667664 B chain DGSPDVTTADIGANTPDA
PGRP2_HUMAN N-acetylmuramoyl-L- 0.034738338 TK alanine amidase
QLGLPGPPDVPDHAAYHPF ITIH4_HUMAN Inter-alpha-trypsin 0.043130591
inhibitor heavy chain H4 FPLGSYTIQNIVAGSTYLF LCAP_HUMAN
Leucyl-cystinyl 0.044698045 STK aminopeptidase AHYDLR FETUA_HUMAN
Alpha-2-HS- 0.046259201 glycoprotein SFRPFVPR LBP_HUMAN
Lipopolysaccharide- 0.047948847 binding protein
Example 4
Study III Shotgun Identification of Preterm Birth Biomarkers
[0175] A further study used a hypothesis-independent shotgun
approach to identify and quantify additional biomarkers not present
on our multiplexed hypothesis dependent MRM assay. Samples were
processed as described in the preceding Examples unless noted
below.
[0176] Tryptic digests of MARS depleted patient (preterm birth
cases and term controls) samples were fractionated by
two-dimensional liquid chromatography and analyzed by tandem mass
spectrometry. Aliquots of the samples, equivalent to 3-4 .mu.l of
serum, were injected onto a 6 cm.times.75 .mu.m self-packed strong
cation exchange (Luna SCX, Phenomenex) column. Peptides were eluded
from the SCX column with salt (15, 30, 50, 70, and 100% B, where
B=250 mM ammonium acetate, 2% acetonitrile, 0.1% formic acid in
water) and consecutively for each salt elution, were bound to a 0.5
.mu.l C18 packed stem trap (Optimize Technologies, Inc.) and
further fractionated on a 10 cm.times.75 .mu.m reversed phase
ProteoPep II PicoFrit column (New Objective). Peptides were eluted
from the reversed phase column with an acetonitrile gradient
containing 0.1% formic acid and directly ionized on an LTQ-Orbitrap
(ThermoFisher). For each scan, peptide parent ion masses were
obtained in the Orbitrap at 60K resolution and the top seven most
abundant ions were fragmented in the LTQ to obtain peptide sequence
information.
[0177] Parent and fragment ion data were used to search the Human
RefSeq database using the Sequest (Eng et al., J. Am. Soc. Mass
Spectrom 1994; 5:976-989) and X!Tandem (Craig and Beavis,
Bioinformatics 2004; 20:1466-1467) algorithms. For Sequest, data
was searched with a 20 ppm tolerance for the parent ion and 1 AMU
for the fragment ion. Two missed trypsin cleavages were allowed,
and modifications included static cysteine carboxyamidomethylation
and methionine oxidation. After searching the data was filtered by
charge state vs. Xcorr scores (charge+1.gtoreq.1.5 Xcorr, charge+2
.gtoreq.2.0, charge+3.gtoreq.2.5). Similar search parameters were
used for X!tandem, except the mass tolerance for the fragment ion
was 0.8 AMU and there is no Xcorr filtering. Instead, the
PeptideProphet algorithm (Keller et al., Anal. Chem
2002;74:5383-5392) was used to validate each X!Tandem
peptide-spectrum assignment and Protein assignments were validated
using ProteinProphet algorithm (Nesvizhskii et al., Anal. Chem
2002; 74:5383-5392). Data was filtered to include only the
peptide-spectrum matches that had PeptideProphet probability of 0.9
or more. After compiling peptide and protein identifications,
spectral count data for each peptide were imported into DAnTE
software (Polpitiya et al., Bioinformatics. 2008; 24:1556-1558).
Log transformed data was mean centered and missing values were
filtered, by requiring that a peptide had to be identified in at
least 4 cases and 4 controls. To determine the significance of an
analyte, Receiver Operating Characteristic (ROC) curves for each
analyte were created where the true positive rate (Sensitivity) is
plotted as a function of the false positive rate (1-Specificity)
for different thresholds that separate the SPTB and Term groups.
The area under the ROC curve (AUC) is equal to the probability that
a classifier will rank a randomly chosen positive instance higher
than a randomly chosen negative one. Peptides with AUC greater than
or equal to 0.6 found uniquely by Sequest or Xtandem are found in
Tables 8 and 9, respectively, and those identified by both
approaches are found in Table 10.
TABLE-US-00009 TABLE 8 Significant peptides (AUC >0.6) for
Sequest only Protein Description Uniprot ID (name) Peptide S_AUC
5'-AMP-activated Q9UGI9 (AAKG3_HUMAN) K.LVIFDTM*LEIK.K 0.78 protein
kinase subunit gamma-3 afamin precursor P43652 (AFAM_HUMAN) K.
FIEDNIEYITIIAFAQYVQEATFEEME 0.79 K.L afamin precursor P43652
(AFAM_HUMAN) K.IAPQLSTEELVSLGEK.M 0.71 afamin precursor P43652
(AFAM_HUMAN) K.LKHELTDEELQSLFTNFANVVDK.C 0.60 afamin precursor
P43652 (AFAM_HUMAN) K.LPNNVLQEK.I 0.60 afamin precursor P43652
(AFAM_HUMAN) K.SDVGFLPPFPTLDPEEK.C 0.71 afamin precursor P43652
(AFAM_HUMAN) K.VMNHICSK.Q 0.68 afamin precursor P43652 (AFAM_HUMAN)
R.ESLLNHFLYEVAR.R 0.69 afamin precursor P43652 (AFAM_HUMAN)
R.LCFFYNKK.S 0.69 alpha-1- P01011 (AACT_HUMAN)
K.AVLDVFEEGTEASAATAVK.I 0.72 antichymotrypsin precursor alpha-1-
P01011 (AACT_HUMAN) K.EQLSLLDR.F 0.65 antichymotrypsin precursor
alpha-1- P01011 (AACT_HUMAN) K.EQLSLLDRFTEDAK.R 0.64
antichymotrypsin precursor alpha-1- P01011 (AACT_HUMAN)
K.EQLSLLDRFTEDAKR.L 0.60 antichymotrypsin precursor alpha-1- P01011
(AACT_HUMAN) K.ITDLIKDLDSQTMM*VLVNYIFFK.A 0.65 antichymotrypsin
precursor alpha-1- P01011 (AACT_HUMAN) K.ITLLSALVETR.T 0.62
antichymotrypsin precursor alpha-1- P01011 (AACT_HUMAN)
K.RLYGSEAFATDFQDSAAAK.K 0.62 antichymotrypsin precursor alpha-1-
P01011 (AACT_HUMAN) R.EIGELYLPK.F 0.65 antichymotrypsin precursor
alpha-1B- P04217 (A1BG_HUMAN) R.CEGPIPDVTFELLR.E 0.67 glycoprotein
precursor alpha-1B- P04217 (A1BG_HUMAN) R.FALVR.E 0.79 glycoprotein
precursor alpha-2-antiplasmin P08697 (A2AP_HUMAN) K.SPPGVCSR.D 0.81
isoform a precursor alpha-2-antiplasmin P08697 (A2AP_HUMAN)
R.DSFHLDEQFTVPVEMMQAR.T 0.69 isoform a precursor alpha-2-HS- P02765
(FETUA_HUMAN) K.CNLLAEK.Q 0.67 glycoprotein preproprotein
alpha-2-HS- P02765 (FETUA_HUMAN) K.EHAVEGDCDFQLLK.L 0.67
glycoprotein preproprotein alpha-2-HS- P02765 (FETUA_HUMAN)
K.HTLNQIDEVKVWPQQPSGELFEIEID 0.64 glycoprotein TLETTCHVLDPTPVAR.C
preproprotein alpha-2- P01023 (A2MG_HUMAN) K.MVSGFIPLKPTVK.M 0.73
macroglobulin precursor alpha-2- P01023 (A2MG_HUMAN)
R.AFQPFFVELTM*PYSVIR.G 0.68 macroglobulin precursor alpha-2- P01023
(A2MG_HUMAN) R.AFQPFFVELTMPYSVIR.G 0.62 macroglobulin precursor
alpha-2- P01023 (A2MG_HUMAN) R.NQGNTWLTAFVLK.T 0.73 macroglobulin
precursor angiotensinogen P01019 (ANGT_HUMAN) K.IDRFMQAVTGWK.T 0.81
preproprotein angiotensinogen P01019 (ANGT_HUMAN) K.LDTEDKLR.A 0.72
preproprotein angiotensinogen P01019 (ANGT_HUMAN)
K.TGCSLMGASVDSTLAFNTYVHFQGK 0.64 preproprotein .M angiotensinogen
P01019 (ANGT_HUMAN) R.AAMVGMLANFLGFR.I 0.62 preproprotein
antithrombin-III P01008 (ANT3_HUMAN) K.NDNDNIFLSPLSISTAFAMTK.L 0.64
precursor antithrombin-III P01008 (ANT3_HUMAN)
K.SKLPGIVAEGRDDLYVSDAFHK.A 0.81 precursor antithrombin-III P01008
(ANT3_HUMAN) R.EVPLNTIIFMGR.V 0.61 precursor antithrombin-III
P01008 (ANT3_HUMAN) R.FATTFYQHLADSKNDNDNIFLSPLSIS 0.66 precursor
TAFAMTK.L antithrombin-III P01008 (ANT3_HUMAN)
R.ITDVIPSEAINELTVLVLVNTIYFK.G 0.60 precursor antithrombin-III
P01008 (ANT3_HUMAN) R.RVWELSK.A 0.63 precursor antithrombin-III
P01008 (ANT3_HUMAN) R.VAEGTQVLELPFKGDDITM*VLILPK 0.62 precursor
PEK.S antithrombin-III P01008 (ANT3_HUMAN)
R.VAEGTQVLELPFKGDDITMVLILPKP 0.62 precursor EK.S apolipoprotein
A-II P02652 (APOA2_HUMAN) K.AGTELVNFLSYFVELGTQPATQ.- 0.61
preproprotein apolipoprotein A-II P02652 (APOA2_HUMAN)
K.EPCVESLVSQYFQTVTDYGK.D 0.63 preproprotein apolipoprotein A-IV
P06727 (APOA4_HUMAN) K.ALVQQMEQLR.Q 0.61 precursor apolipoprotein
A-IV P06727 (APOA4_HUMAN) K.LGPHAGDVEGHLSFLEK.D 0.61 precursor
apolipoprotein A-IV P06727 (APOA4_HUMAN) K.SELTQQLNALFQDK.L 0.71
precursor apolipoprotein A-IV P06727 (APOA4_HUMAN)
K.SLAELGGHLDQQVEEFRR.R 0.61 precursor apolipoprotein A-IV P06727
(APOA4_HUMAN) K.VKIDQTVEELRR.S 0.75 precursor apolipoprotein A-IV
P06727 (APOA4_HUMAN) K.VNSFFSTFK.E 0.63 precursor apolipoprotein
B-100 P04114 (APOB_HUMAN) K.ATFQTPDFIVPLTDLR.I 0.65 precursor
apolipoprotein B-100 P04114 (APOB_HUMAN) K.AVSM*PSFSILGSDVR.V 0.65
precursor apolipoprotein B-100 P04114 (APOB_HUMAN)
K.AVSMPSFSILGSDVR.V 0.67 precursor apolipoprotein B-100 P04114
(APOB_HUMAN) K.EQHLFLPFSYK.N 0.65 precursor apolipoprotein B-100
P04114 (APOB_HUMAN) K.KIISDYHQQFR.Y 0.63 precursor apolipoprotein
B-100 P04114 (APOB_HUMAN) K.QVFLYPEKDEPTYILNIK.R 0.64 precursor
apolipoprotein B-100 P04114 (APOB_HUMAN) K.SPAFTDLHLR.Y 0.69
precursor apolipoprotein B-100 P04114 (APOB_HUMAN)
K.TILGTMPAFEVSLQALQK.A 0.62 precursor apolipoprotein B-100 P04114
(APOB_HUMAN) K.VLADKFIIPGLK.L 0.72 precursor apolipoprotein B-100
P04114 (APOB_HUMAN) K.YSQPEDSLIPFFEITVPESQLTVSQFTL 0.61 precursor
PK.S apolipoprotein B-100 P04114 (APOB_HUMAN) R.DLKVEDIPLAR.I 0.64
precursor apolipoprotein B-100 P04114 (APOB_HUMAN)
R.GIISALLVPPETEEAK.Q 0.81 precursor apolipoprotein B-100 P04114
(APOB_HUMAN) R.ILGEELGFASLHDLQLLGK.L 0.62 precursor apolipoprotein
B-100 P04114 (APOB_HUMAN) R.LELELRPTGEIEQYSVSATYELQR.E 0.60
precursor apolipoprotein B-100 P04114 (APOB_HUMAN)
R.NIQEYLSILTDPDGK.G 0.68 precursor apolipoprotein B-100 P04114
(APOB_HUMAN) R.TFQIPGYTVPVVNVEVSPFTIEMSAF 0.75 precursor GYVFPK.A
apolipoprotein B-100 P04114 (APOB_HUMAN) R.TIDQMLNSELQWPVPDIYLR.D
0.70 precursor apolipoprotein C-I P02654 (APOC1_HUMAN)
K.MREWFSETFQK.V 0.61 precursor apolipoprotein C-II P02655
(APOC2_HUMAN) K.STAAMSTYTGIFTDQVLSVLKGEE.- 0.61 precursor
apolipoprotein C-III P02656 (APOC3_HUMAN) R.GWVTDGFSSLK.D 0.62
precursor apolipoprotein E P02649 (APOE_HUMAN) R.AATVGSLAGQPLQER.A
0.61 precursor apolipoprotein E P02649 (APOE_HUMAN)
R.LKSWFEPLVEDMQR.Q 0.65 precursor apolipoprotein E P02649
(APOE_HUMAN) R.WVQTLSEQVQEELLSSQVTQELR.A 0.64 precursor ATP-binding
cassette O14678 (ABCD4_HUMAN) K.LCGGGRWELM*R.I 0.60 sub-family D
member 4 ATP-binding cassette Q9NUQ8 (ABCF3_HUMAN) K.LPGLLK.R 0.73
sub-family F member 3 beta-2-glycoprotein 1 P02749 (APOH_HUMAN)
K.EHSSLAFWK.T 0.64 precursor beta-2-glycoprotein 1 P02749
(APOH_HUMAN) R.TCPKPDDLPFSTVVPLK.T 0.60 precursor
beta-2-glycoprotein 1 P02749 (APOH_HUMAN) R.VCPFAGILENGAVR.Y 0.68
precursor beta-Ala-His Q96KN2 (CNDP1_HUMAN) K.LFAAFFLEMAQLH.- 0.68
dipeptidase
precursor biotinidase precursor P43251 (BTD_HUMAN) K.SHLIIAQVAK.N
0.62 carboxypeptidase B2 Q96IY4 (CBPB2_HUMAN) K.NAIWIDCGIHAR.E 0.62
preproprotein carboxypeptidase N P15169 (CBPN_HUMAN)
R.EALIQFLEQVHQGIK.G 0.69 catalytic chain precursor carboxypeptidase
N P22792 (CPN2_HUMAN) R.LLNIQTYCAGPAYLK.G 0.62 subunit 2 precursor
catalase P04040 (CATA_HUMAN) R.LCENIAGHLKDAQIFIQK.K 0.62
ceruloplasmin P00450 (CERU_HUMAN) K.AETGDKVYVHLK.N 0.61 precursor
ceruloplasmin P00450 (CERU_HUMAN) K.AGLQAFFQVQECNK.S 0.62 precursor
ceruloplasmin P00450 (CERU_HUMAN) K.DIASGLIGPLIICK.K 0.63 precursor
ceruloplasmin P00450 (CERU_HUMAN) K.DIFTGLIGPM*K.I 0.63 precursor
ceruloplasmin P00450 (CERU_HUMAN) K.DIFTGLIGPMK.I 0.68 precursor
ceruloplasmin P00450 (CERU_HUMAN) K.M*YYSAVDPTKDIFTGLIGPMK.I 0.62
precursor ceruloplasmin P00450 (CERU_HUMAN)
K.MYYSAVDPTKDIFTGLIGPM*K.I 0.63 precursor ceruloplasmin P00450
(CERU_HUMAN) K.PVWLGFLGPIIK.A 0.63 precursor ceruloplasmin P00450
(CERU_HUMAN) R.ADDKVYPGEQYTYMLLATEEQSPGE 0.64 precursor GDGNCVTR.I
ceruloplasmin P00450 (CERU_HUMAN) R.DTANLFPQTSLTLHM*WPDTEGTF 0.71
precursor NVECLTTDHYTGGMK.Q ceruloplasmin P00450 (CERU_HUMAN)
R.DTANLFPQTSLTLHMWPDTEGTFN 0.68 precursor VECLTTDHYTGGMK.Q
ceruloplasmin P00450 (CERU_HUMAN) R.FNKNNEGTYYSPNYNPQSR.S 0.74
precursor ceruloplasmin P00450 (CERU_HUMAN)
R.IDTINLFPATLFDAYM*VAQNPGEW 0.75 precursor M*LSCQNLNHLK.A
ceruloplasmin P00450 (CERU_HUMAN) R.IDTINLFPATLFDAYM*VAQNPGEW 0.86
precursor MLSCQNLNHLK.A ceruloplasmin P00450 (CERU_HUMAN)
R.IDTINLFPATLFDAYMVAQNPGEW 0.60 precursor M*LSCQNLNHLK.A
ceruloplasmin P00450 (CERU_HUMAN) R.KAEEEHLGILGPQLHADVGDKVK.I 0.71
precursor ceruloplasmin P00450 (CERU_HUMAN) R.TTIEKPVWLGFLGPIIK.A
0.63 precursor cholinesterase P06276 (CHLE_HUMAN) R.FWTSFFPK.V 0.76
precursor clusterin P10909 (CLUS_HUMAN) K.LFDSDPITVTVPVEVSR.K 0.78
preproprotein clusterin P10909 (CLUS_HUMAN) R.ASSIIDELFQDR.F 0.68
preproprotein coagulation factor IX P00740 (FA9_HUMAN)
K.WIVTAAHCVETGVK.I 0.60 preproprotein coagulation factor VII P08709
(FA7_HUMAN) R.FSLVSGWGQLLDR.G 0.78 isoform a preproprotein
coagulation factor X P00742 (FA10_HUMAN) K.ETYDFDIAVLR.L 0.75
preproprotein coiled-coil domain- Q8IYE1 (CCD13_HUMAN)
K.VRQLEMEIGQLNVHYLR.N 0.67 containing protein 13 complement C1q
P02745 (C1QA_HUMAN) R.PAFSAIR.R 0.66 subcomponent subunit A
precursor complement C1q P02746 (C1QB_HUMAN)
K.VVTFCDYAYNTFQVTTGGMVLK.L 0.63 subcomponent subunit B precursor
complement C1q P02747 (C1QC_HUMAN) K.FQSVFTVTR.Q 0.63 subcomponent
subunit C precursor complement C1r P00736 (C1R_HUMAN)
K.TLDEFTIIQNLQPQYQFR.D 0.62 subcomponent precursor complement C1r
P00736 (C1R_HUMAN) R.MDVFSQNMFCAGHPSLK.Q 0.68 subcomponent
precursor complement C1r P00736 (C1R_HUMAN) R.WILTAAHTLYPK.E 0.74
subcomponent precursor complement C1s P09871 (C1S_HUMAN)
K.FYAAGLVSWGPQCGTYGLYTR.V 0.68 subcomponent precursor complement
C1s P09871 (C1S_HUMAN) K.GFQVVVTLR.R 0.63 subcomponent precursor
complement C2 P06681 (CO2_HUMAN) R.GALISDQWVLTAAHCFR.D 0.61 isoform
3 complement C2 P06681 (CO2_HUMAN) R.PICLPCTMEANLALR.R 0.66 isoform
3 complement C3 P01024 (CO3_HUMAN) R.YYGGGYGSTQATFMVFQALAQYQK 0.75
precursor .D complement C4-A P0C0L4 (CO4A_HUMAN) K.GLCVATPVQLR.V
0.74 isoform 1 complement C4-A P0C0L4 (CO4A_HUMAN)
K.M*RPSTDTITVM*VENSHGLR.V 0.83 isoform 1 complement C4-A P0C0L4
(CO4A_HUMAN) K.MRPSTDTITVM*VENSHGLR.V 0.72 isoform 1 complement
C4-A P0C0L4 (CO4A_HUMAN) K.VGLSGM*AIADVTLLSGFHALR.A 0.71 isoform 1
complement C4-A P0C0L4 (CO4A_HUMAN) K.VLSLAQEQVGGSPEK.L 0.63
isoform 1 complement C4-A P0C0L4 (CO4A_HUMAN) R.EMSGSPASGIPVK.V
0.65 isoform 1 complement C4-A P0C0L4 (CO4A_HUMAN)
R.GCGEQTM*IYLAPTLAASR.Y 0.75 isoform 1 complement C4-A P0C0L4
(CO4A_HUMAN) R.GLQDEDGYR.M 0.75 isoform 1 complement C4-A P0C0L4
(CO4A_HUMAN) R.GQIVFMNREPK.R 0.93 isoform 1 complement C4-A P0C0L4
(CO4A_HUMAN) R.KKEVYM*PSSIFQDDFVIPDISEPGT 0.72 isoform 1 WK.I
complement C4-A P0C0L4 (CO4A_HUMAN) R.LPMSVR.R 0.78 isoform 1
complement C4-A P0C0L4 (CO4A_HUMAN) R.LTVAAPPSGGPGFLSIER.P 0.84
isoform 1 complement C4-A P0C0L4 (CO4A_HUMAN) R.NFLVR.A 0.75
isoform 1 complement C4-A P0C0L4 (CO4A_HUMAN)
R.NGESVKLHLETDSLALVALGALDTAL 0.88 isoform 1 YAAGSK.S complement
C4-A P0C0L4 (CO4A_HUMAN) R.QGSFQGGFR.S 0.60 isoform 1 complement
C4-A P0C0L4 (CO4A_HUMAN) R.TLEIPGNSDPNMIPDGDFNSYVR.V 0.69 isoform 1
complement C4-A P0C0L4 (CO4A_HUMAN) R.VTASDPLDTLGSEGALSPGGVASLLR
0.63 isoform 1 .L complement C4-A P0C0L4 (CO4A_HUMAN)
R.YLDKTEQWSTLPPETK.D 0.67 isoform 1 complement C5 P01031
(CO5_HUMAN) K.ADNFLLENTLPAQSTFTLAISAYALSL 0.63 preproprotein GDK.T
complement C5 P01031 (CO5_HUMAN) K.ALVEGVDQLFTDYQIK.D 0.63
preproprotein complement C5 P01031 (CO5_HUMAN)
K.DGHVILQLNSIPSSDFLCVR.F 0.62 preproprotein complement C5 P01031
(CO5_HUMAN) K.DVFLEMNIPYSVVR.G 0.63 preproprotein complement C5
P01031 (CO5_HUMAN) K.EFPYRIPLDLVPK.T 0.60 preproprotein complement
C5 P01031 (CO5_HUMAN) K.FQNSAILTIQPK.Q 0.67 preproprotein
complement C5 P01031 (CO5_HUMAN) K.VFKDVFLEMNIPYSVVR.G 0.63
preproprotein complement C5 P01031 (CO5_HUMAN) R.VFQFLEK.S 0.61
preproprotein complement P13671 (CO6_HUMAN) K.DLHLSDVFLK.A 0.60
component C6 precursor complement P13671 (CO6_HUMAN)
R.TECIKPVVQEVLTITPFQR.L 0.62 component C6 precursor complement
P10643 (CO7_HUMAN) K.SSGWHFVVK.F 0.61 component C7 precursor
complement P10643 (CO7_HUMAN) R.ILPLTVCK.M 0.75 component C7
precursor complement P07357 (CO8A_HUMAN) R.ALDQYLMEFNACR.C 0.65
component C8 alpha chain precursor complement P07360 (CO8G_HUMAN)
K.YGFCEAADQFHVLDEVR.R 0.60 component C8 gamma chain precursor
complement P02748 (CO9_HUMAN) R.AIEDYINEFSVRK.0 0.69 component C9
precursor complement P02748 (CO9_HUMAN)
R.TAGYGINILGMDPLSTPFDNEFYNGL 0.69 component C9 CNR.D precursor
complement factor B P00751 (CFAB_HUMAN) K.ALFVSEEEKK.L 0.64
preproprotein complement factor B P00751 (CFAB_HUMAN) K.CLVNLIEK.V
0.70 preproprotein complement factor B P00751 (CFAB_HUMAN)
K.EAGIPEFYDYDVALIK.L 0.66 preproprotein complement factor B P00751
(CFAB_HUMAN) K.VSEADSSNADWVTK.Q 0.73
preproprotein complement factor B P00751 (CFAB_HUMAN)
K.YGQTIRPICLPCTEGTTR.A 0.67 preproprotein complement factor B
P00751 (CFAB_HUMAN) R.DLEIEVVLFHPNYNINGK.K 0.71 preproprotein
complement factor B P00751 (CFAB_HUMAN) R.FLCTGGVSPYADPNTCR.G 0.64
preproprotein complement factor H P08603 (CFAH_HUMAN)
K.DGWSAQPTCIK.S 0.80 isoform a precursor complement factor H P08603
(CFAH_HUMAN) K.EGWIHTVCINGR.W 0.67 isoform a precursor complement
factor H P08603 (CFAH_HUMAN) K.TDCLSLPSFENAIPMGEK.K 0.61 isoform a
precursor complement factor H P08603 (CFAH_HUMAN)
R.DTSCVNPPTVQNAYIVSR.Q 0.60 isoform a precursor complement factor H
P08603 (CFAH_HUMAN) K.CTSTGWIPAPR.0 0.68 isoform b precursor
complement factor H P08603 (CFAH_HUMAN) K.IIYKENER.F 0.76 isoform b
precursor complement factor H P08603 (CFAH_HUMAN)
K.IVSSAM*EPDREYHFGQAVR.F 0.75 isoform b precursor complement factor
H P08603 (CFAH_HUMAN) K.IVSSAMEPDREYHFGQAVR.F 0.68 isoform b
precursor complement factor H P08603 (CFAH_HUMAN) R.CTLKPCDYPDIK.H
0.81 isoform b precursor complement factor H P08603 (CFAH_HUMAN)
R.KGEWVALNPLR.K 0.60 isoform b precursor complement factor H P08603
(CFAH_HUMAN) R.KGEWVALNPLRK.0 0.69 isoform b precursor complement
factor H P08603 (CFAH_HUMAN) R.RPYFPVAVGK.Y 0.68 isoform b
precursor complement factor Q03591 (FHR1_HUMAN) R.EIMENYNIALR.W
0.64 H-related protein 1 precursor complement factor I P05156
(CFAI_HUMAN) K.DASGITCGGIYIGGCWILTAAHCLR.A 0.71 preproprotein
complement factor I P05156 (CFAI_HUMAN) K.VANYFDWISYHVGR.P 0.72
preproprotein complement factor I P05156 (CFAI_HUMAN)
R.IIFHENYNAGTYQNDIALIEMK.K 0.63 preproprotein complement factor I
P05156 (CFAI_HUMAN) R.YQIWTTVVDWIHPDLK.R 0.63 preproprotein
conserved oligomeric Q9Y2V7 (COG6_HUMAN) K.ISNLLK.F 0.65 Golgi
complex subunit 6 isoform corticosteroid- P08185 (CBG_HUMAN)
R.WSAGLTSSQVDLYIPK.V 0.62 binding globulin precursor C-reactive
protein P02741 (CRP_HUMAN) K.YEVQGEVFTKPQLWP.- 0.60 precursor
dopamine beta- P09172 (DOPO_HUMAN) R.HVLAAWALGAK.A 0.88 hydroxylase
precursor double-stranded Q9NS39 (RED2_HUMAN) R.AGLRYVCLAEPAER.R
0.75 RNA-specific editase B2 dual oxidase 2 Q9NRD8 (DUOX2_HUMAN)
R.FTQLCVKGGGGGGNGIR.D 0.65 precursor FERM domain- Q9BZ67
(FRMD8_HUMAN) R.VQLGPYQPGRPAACDLR.E 0.65 containing protein 8
fetuin-B precursor Q9UGM5 (FETUB_HUMAN) R.GGLGSLFYLTLDVLETDCHVLR.K
0.83 ficolin-3 isoform 1 O75636 (FCN3_HUMAN)
R.ELLSQGATLSGWYHLCLPEGR.A 0.69 precursor gastric intrinsic factor
P27352 (IF_HUMAN) K.KTTDM*ILNEIKQGK.F 0.60 precursor gelsolin
isoform d P06396 (GELS_HUMAN) K.NWRDPDQTDGLGLSYLSSHIANVER 0.72 .V
gelsolin isoform d P06396 (GELS_HUMAN) K.TPSAAYLWVGTGASEAEK.T 0.80
gelsolin isoform d P06396 (GELS_HUMAN) R.VEKFDLVPVPTNLYGDFFTGDAYVIL
0.60 K.T gelsolin isoform d P06396 (GELS_HUMAN)
R.VPFDAATLHTSTAMAAQHGMDDD 0.67 GTGQK.Q glutathione P22352
(GPX3_HUMAN) K.FYTFLK.N 0.63 peroxidase 3 precursor hemopexin
precursor P02790 (HEMO_HUMAN) K.GDKVWVYPPEKK.E 0.65 hemopexin
precursor P02790 (HEMO_HUMAN) K.LLQDEFPGIPSPLDAAVECHR.G 0.71
hemopexin precursor P02790 (HEMO_HUMAN) K.SGAQATWTELPWPHEK.V 0.64
hemopexin precursor P02790 (HEMO_HUMAN) K.SGAQATWTELPWPHEKVDGALCM
0.61 EK.S hemopexin precursor P02790 (HEMO_HUMAN) K.VDGALCMEK.S
0.66 hemopexin precursor P02790 (HEMO_HUMAN) R.DYFMPCPGR.G 0.68
hemopexin precursor P02790 (HEMO_HUMAN) R.EWFWDLATGTM*K.E 0.64
hemopexin precursor P02790 (HEMO_HUMAN) R.QGHNSVFLIK.G 0.71 heparin
cofactor 2 P05546 (HEP2_HUMAN) K.HQGTITVNEEGTQATTVTTVGFMPL 0.60
precursor STQVR.F heparin cofactor 2 P05546 (HEP2_HUMAN)
K.YEITTIHNLFR.K 0.62 precursor heparin cofactor 2 P05546
(HEP2_HUMAN) R.LNILNAK.F 0.68 precursor heparin cofactor 2 P05546
(HEP2_HUMAN) R.NFGYTLR.S 0.64 precursor heparin cofactor 2 P05546
(HEP2_HUMAN) R.VLKDQVNTFDNIFIAPVGISTAMGM 0.63 precursor *ISLGLK.G
hepatocyte cell Q14CZ8 (HECAM_HUMAN) K.PLLNDSRMLLSPDQK.V 0.61
adhesion molecule precursor hepatocyte growth Q04756 (HGFA_HUMAN)
R.VQLSPDLLATLPEPASPGR.Q 0.82 factor activator preproprotein
histidine-rich P04196 (HRG_HUMAN) R.DGYLFQLLR.I 0.63 glycoprotein
precursor hyaluronan-binding Q14520 (HABP2_HUMAN) K.FLNWIK.A 0.82
protein 2 isoform 1 preproprotein hyaluronan-binding Q14520
(HABP2_HUMAN) K.LKPVDGHCALESK.Y 0.61 protein 2 isoform 1
preproprotein hyaluronan-binding Q14520 (HABP2_HUMAN)
K.RPGVYTQVTK.F 0.74 protein 2 isoform 1 preproprotein inactive
caspase-12 Q6UXS9 (CASPC_HUMAN) K.AGADTHGRLLQGNICNDAVTK.A 0.74
insulin-degrading P14735 (IDE_HUMAN) K.KIIEKM*ATFEIDEK.R 0.85
enzyme isoform 1 insulin-like growth P35858 (ALS_HUMAN)
R.SFEGLGQLEVLTLDHNQLQEVK.A 0.62 factor-binding protein complex acid
labile subunit isoform 2 precursor inter-alpha-trypsin P19827
(ITIH1_HUMAN) K.ELAAQTIKK.S 0.81 inhibitor heavy chain H1 isoform a
precursor inter-alpha-trypsin P19827 (ITIH1_HUMAN)
K.GSLVQASEANLQAAQDFVR.G 0.71 inhibitor heavy chain H1 isoform a
precursor inter-alpha-trypsin P19827 (ITIH1_HUMAN)
K.QLVHHFEIDVDIFEPQGISK.L 0.70 inhibitor heavy chain H1 isoform a
precursor inter-alpha-trypsin P19827 (ITIH1_HUMAN)
K.QYYEGSEIVVAGR.I 0.83 inhibitor heavy chain H1 isoform a precursor
inter-alpha-trypsin P19827 (ITIH1_HUMAN)
R.EVAFDLEIPKTAFISDFAVTADGNAFI 0.70 inhibitor heavy chain GDIK.D H1
isoform a precursor inter-alpha-trypsin P19827 (ITIH1_HUMAN)
R.GMADQDGLKPTIDKPSEDSPPLEM* 0.63 inhibitor heavy chain LGPR.R H1
isoform a precursor inter-alpha-trypsin P19827 (ITIH1_HUMAN)
R.GMADQDGLKPTIDKPSEDSPPLEML 0.60 inhibitor heavy chain GPR.R H1
isoform a precursor inter-alpha-trypsin P19823 (ITIH2_HUMAN)
K.FDPAKLDQIESVITATSANTQLVLETL 0.80 inhibitor heavy chain
AQM*DDLQDFLSK.D H2 precursor inter-alpha-trypsin P19823
(ITIH2_HUMAN) K.KFYNQVSTPLLR.N 0.76 inhibitor heavy chain H2
precursor inter-alpha-trypsin P19823 (ITIH2_HUMAN)
K.NILFVIDVSGSM*WGVK.M 0.68 inhibitor heavy chain H2 precursor
inter-alpha-trypsin P19823 (ITIH2_HUMAN) K.NILFVIDVSGSMWGVK.M 0.62
inhibitor heavy chain H2 precursor inter-alpha-trypsin P19823
(ITIH2_HUMAN) R.KLGSYEHR.I 0.72 inhibitor heavy chain H2 precursor
inter-alpha-trypsin P19823 (ITIH2_HUMAN) R.LSNENHGIAQR.I 0.66
inhibitor heavy chain H2 precursor inter-alpha-trypsin P19823
(ITIH2_HUMAN) R.MATTMIQSK.V 0.60 inhibitor heavy chain H2 precursor
inter-alpha-trypsin P19823 (ITIH2_HUMAN)
R.SILQM*SLDHHIVTPLTSLVIENEAG 0.63 inhibitor heavy chain DER.M H2
precursor inter-alpha-trypsin P19823 (ITIH2_HUMAN)
R.SILQMSLDHHIVTPLTSLVIENEAGDE 0.65
inhibitor heavy chain R.M H2 precursor inter-alpha-trypsin P19823
(ITIH2_HUMAN) R.TEVNVLPGAK.V 0.69 inhibitor heavy chain H2
precursor inter-alpha-trypsin Q14624 (ITIH4_HUMAN) K.NVVFVIDK.S
0.68 inhibitor heavy chain H4 isoform 1 precursor
inter-alpha-trypsin Q14624 (ITIH4_HUMAN) K.WKETLFSVMPGLK.M 0.65
inhibitor heavy chain H4 isoform 1 precursor inter-alpha-trypsin
Q14624 (ITIH4_HUMAN) K.YIFHNFM*ER.L 0.67 inhibitor heavy chain H4
isoform 1 precursor inter-alpha-trypsin Q14624 (ITIH4_HUMAN)
R.FAHTVVTSR.V 0.63 inhibitor heavy chain H4 isoform 1 precursor
inter-alpha-trypsin Q14624 (ITIH4_HUMAN) R.FKPTLSQQQK.S 0.60
inhibitor heavy chain H4 isoform 1 precursor inter-alpha-trypsin
Q14624 (ITIH4_HUMAN) R.IHEDSDSALQLQDFYQEVANPLLTA 0.64 inhibitor
heavy chain VTFEYPSNAVEEVTQNNFR.L H4 isoform 1 precursor
inter-alpha-trypsin Q14624 (ITIH4_HUMAN) R.MNFRPGVLSSR.Q 0.63
inhibitor heavy chain H4 isoform 1 precursor inter-alpha-trypsin
Q14624 (ITIH4_HUMAN) R.NVHSAGAAGSR.M 0.62 inhibitor heavy chain H4
isoform 1 precursor inter-alpha-trypsin Q14624 (ITIH4_HUMAN)
R.NVHSGSTFFK.Y 0.75 inhibitor heavy chain H4 isoform 1 precursor
inter-alpha-trypsin Q14624 (ITIH4_HUMAN) R.RLGVYELLLK.V 0.66
inhibitor heavy chain H4 isoform 1 precursor kallistatin precursor
P29622 (KAIN_HUMAN) K.KLELHLPK.F 0.78 kallistatin precursor P29622
(KAIN_HUMAN) R.EIEEVLTPEMLMR.W 0.60 kininogen-1 isoform 2 P01042
(KNG1_HUMAN) K.AATGECTATVGKR.S 0.67 precursor kininogen-1 isoform 2
P01042 (KNG1_HUMAN) K.LGQSLDCNAEVYVVPWEK.K 0.72 precursor
kininogen-1 isoform 2 P01042 (KNG1_HUMAN) K.YNSQNQSNNQFVLYR.I 0.62
precursor kininogen-1 isoform 2 P01042 (KNG1_HUMAN) R.QVVAGLNFR.I
0.64 precursor leucine-rich alpha-2- P02750 (A2GL_HUMAN)
K.DLLLPQPDLR.Y 0.64 glycoprotein precursor leucine-rich alpha-2-
P02750 (A2GL_HUMAN) R.LHLEGNKLQVLGK.D 0.76 glycoprotein precursor
leucine-rich alpha-2- P02750 (A2GL_HUMAN) R.TLDLGENQLETLPPDLLR.G
0.61 glycoprotein precursor lipopolysaccharide- P18428 (LBP_HUMAN)
K.GLQYAAQEGLLALQSELLR.I 0.82 binding protein precursor
lipopolysaccharide- P18428 (LBP_HUMAN) K.LAEGFPLPLLK.R 0.66 binding
protein precursor lumican precursor P51884 (LUM_HUMAN)
K.SLEYLDLSFNQIAR.L 0.65 lumican precursor P51884 (LUM_HUMAN)
R.LKEDAVSAAFK.G 0.74 m7GpppX Q96C86 (DCPS_HUMAN)
R.IVFENPDPSDGFVLIPDLK.W 0.62 diphosphatase matrix Q99542
(MMP19_HUMAN) R.VYFFK.G 0.63 metalloproteinase-19 isoform 1
preproprotein MBT domain- Q05BQ5 (MBTD1_HUMAN) K.WFDYLR.E 0.65
containing protein 1 monocyte P08571 (CD14_HUMAN)
R.LTVGAAQVPAQLLVGALR.V 0.66 differentiation antigen CD14 precursor
pappalysin-1 Q13219 (PAPP1_HUMAN) R.VSFSSPLVAISGVALR.S 0.66
preproprotein phosphatidylinositol- P80108 (PHLD_HUMAN)
K.GIVAAFYSGPSLSDKEK.L 0.71 glycan-specific phospholipase D
precursor phosphatidylinositol- P80108 (PHLD_HUMAN)
R.WYVPVKDLLGIYEK.L 0.71 glycan-specific phospholipase D precursor
pigment epithelium- P36955 (PEDF_HUMAN) K.LQSLFDSPDFSK.I 0.61
derived factor precursor pigment epithelium- P36955 (PEDF_HUMAN)
R.ALYYDLISSPDIHGTYK.E 0.72 derived factor precursor plasma
kallikrein P03952 (KLKB1_HUMAN) R.CLLFSFLPASSINDMEKR.F 0.60
preproprotein plasma protease C1 P05155 (IC1_HUMAN) K.FQPTLLTLPR.I
0.70 inhibitor precursor plasma protease C1 P05155 (IC1_HUMAN)
K.GVTSVSQIFHSPDLAIR.D 0.66 inhibitor precursor plasminogen isoform
P00747 (PLMN_HUMAN) K.VIPACLPSPNYVVADR.T 0.63 1 precursor
plasminogen isoform P00747 (PLMN_HUMAN) R.FVTWIEGVMR.N 0.60 1
precursor plasminogen isoform P00747 (PLMN_HUMAN) R.HSIFTPETNPR.A
0.63 1 precursor platelet basic protein P02775 (CXCL7_HUMAN)
K.GKEESLDSDLYAELR.C 0.70 preproprotein platelet glycoprotein P40197
(GPV_HUMAN) K.MVLLEQLFLDHNALR.G 0.66 V precursor platelet
glycoprotein P40197 (GPV_HUMAN) R.LVSLDSGLLNSLGALTELQFHR.N 0.88 V
precursor pregnancy zone P20742 (PZP_HUMAN) K.ALLAYAFSLLGK.Q 0.66
protein precursor pregnancy zone P20742 (PZP_HUMAN)
K.DLFHCVSFTLPR.I 0.86 protein precursor pregnancy zone P20742
(PZP_HUMAN) K.MLQITNTGFEMK.L 0.84 protein precursor pregnancy zone
P20742 (PZP_HUMAN) R.NELIPLIYLENPRR.N 0.65 protein precursor
pregnancy zone P20742 (PZP_HUMAN) R.SYIFIDEAHITQSLTWLSQMQK.D 0.68
protein precursor pregnancy-specific P11465 (PSG2_HUMAN)
R.SDPVTLNLLHGPDLPR.I 0.66 beta-1-glycoprotein 2 precursor
pregnancy-specific Q16557 (PSG3_HUMAN) R.TLFLFGVTK.Y 0.62
beta-1-glycoprotein 3 precursor pregnancy-specific Q15238
(PSG5_HUMAN) R.ILILPSVTR.N 0.76 beta-1-glycoprotein 5 precursor
pregnancy-specific Q00889 (PSG6_HUMAN) R.SDPVTLNLLPK.L 0.63
beta-1-glycoprotein 6 isoform a progesterone- Q8WXW3 (PIBF1_HUMAN)
R.VLQLEK.Q 0.71 induced-blocking factor 1 protein AMBP P02760
(AMBP_HUMAN) R.VVAQGVGIPEDSIFTMADR.G 0.60 preproprotein protein
CBFA2T2 O43439 (MTG8R_HUMAN) R.LTEREWADEWKHLDHALNCIMEM 0.70 isoform
MTGR1b VEK.T protein FAM98C Q17RN3 (FA98C_HUMAN)
R.ALCGGDGAAALREPGAGLR.L 0.75 protein NLRC3 Q7RTR2 (NLRC3_HUMAN)
K.ALM*DLLAGKGSQGSQAPQALDR.T 0.92 protein Z-dependent Q9UK55
(ZPI_HUMAN) K.MGDHLALEDYLTTDLVETWLR.N 0.60 protease inhibitor
precursor prothrombin P00734 (THRB_HUMAN) K.SPQELLCGASLISDR.W 0.84
preproprotein prothrombin P00734 (THRB_HUMAN)
R.LAVTTHGLPCLAWASAQAK.A 0.62 preproprotein prothrombin P00734
(THRB_HUMAN) R.SEGSSVNLSPPLEQCVPDR.G 0.70 preproprotein prothrombin
P00734 (THRB_HUMAN) R.SGIECQLWR.S 0.68 preproprotein prothrombin
P00734 (THRB_HUMAN) R.TATSEYQTFFNPR.T 0.60 preproprotein
prothrombin P00734 (THRB_HUMAN) R.VTGWGNLKETWTANVGK.G 0.69
preproprotein putative Q5T013 (HYI_HUMAN) R.IHLM*AGR.V 0.69
hydroxypyruvate isomerase isoform 1 putative Q5T013 (HYI_HUMAN)
R.IHLMAGR.V 0.66 hydroxypyruvate isomerase isoform 1 ras-like
protein family Q92737 (RSLAA_HUMAN) R.PAHPALR.L 0.71 member 10A
precursor ras-related GTP- Q7L523 (RRAGA_HUMAN) K.ISNIIK.Q 0.82
binding protein A retinol-binding P02753 (RET4_HUMAN)
K.M*KYWGVASFLQK.G 0.73 protein 4 precursor retinol-binding P02753
(RET4_HUMAN) R.FSGTWYAM*AK.K 0.63 protein 4 precursor
retinol-binding P02753 (RET4_HUMAN) R.LLNLDGTCADSYSFVFSR.D 0.79
protein 4 precursor
retinol-binding P02753 (RET4_HUMAN) R.LLNNWDVCADMVGTFTDTEDPAKF 0.77
protein 4 precursor K.M sex hormone-binding P04278 (SHBG_HUMAN)
R.LFLGALPGEDSSTSFCLNGLWAQGQ 0.66 globulin isoform 1 R.L precursor
sex hormone-binding P04278 (SHBG_HUMAN) K.DDWFMLGLR.D 0.60 globulin
isoform 4 precursor sex hormone-binding P04278 (SHBG_HUMAN)
R.SCDVESNPGIFLPPGTQAEFNLR.G 0.64 globulin isoform 4 precursor sex
hormone-binding P04278 (SHBG_HUMAN) R.TWDPEGVIFYGDTNPKDDWFM*L 0.65
globulin isoform 4 GLR.D precursor sex hormone-binding P04278
(SHBG_HUMAN) R.TWDPEGVIFYGDTNPKDDWFMLGL 0.66 globulin isoform 4 R.D
precursor signal transducer and P52630 (STAT2_HUMAN)
R.KFCRDIQDPTQLAEMIFNLLLEEK.R 0.73 activator of transcription 2
spectrin beta chain, Q13813 (SPTN1_HUMAN) R.NELIRQEKLEQLAR.R 0.60
non-erythrocytic 1 stabilin-1 precursor Q9NY15 (STAB1_HUMAN)
R.KNLSER.W 0.88 succinate- P51649 (SSDH_HUMAN) R.KWYNLMIQNK.D 0.88
semialdehyde dehydrogenase, mitochondrial tetranectin precursor
P05452 (TETN_HUMAN) K.SRLDTLAQEVALLK.E 0.75 THAP domain- Q8TBB0
(THAP6_HUMAN) K.RLDVNAAGIWEPKK.G 0.69 containing protein 6
thyroxine-binding P05543 (THBG_HUMAN) R.SILFLGK.V 0.79 globulin
precursor tripartite motif- Q9C035 (TRIM5_HUMAN)
R.ELISDLEHRLQGSVM*ELLQGVDGVI 0.60 containing protein 5 K.R vitamin
D-binding P02774 (VTDB_HUMAN) K.EDFTSLSLVLYSR.K 0.66 protein
isoform 1 precursor vitamin D-binding P02774 (VTDB_HUMAN)
K.ELSSFIDKGQELCADYSENTFTEYK.K 0.67 protein isoform 1 precursor
vitamin D-binding P02774 (VTDB_HUMAN)
K.ELSSFIDKGQELCADYSENTFTEYKK.K 0.66 protein isoform 1 precursor
vitamin D-binding P02774 (VTDB_HUMAN) K.EVVSLTEACCAEGADPDCYDTR.T
0.65 protein isoform 1 precursor vitamin D-binding P02774
(VTDB_HUMAN) K.TAMDVFVCTYFMPAAQLPELPDVEL 0.84 protein isoform 1
PTNKDVCDPGNTK.V precursor vitamin D-binding P02774 (VTDB_HUMAN)
R.RTHLPEVFLSK.V 0.69 protein isoform 1 precursor vitamin D-binding
P02774 (VTDB_HUMAN) R.VCSQYAAYGEK.K 0.66 protein isoform 1
precursor vitronectin precursor P04004 (VTNC_HUMAN)
K.LIRDVWGIEGPIDAAFTR.I 0.61 vitronectin precursor P04004
(VTNC_HUMAN) R.DVWGIEGPIDAAFTR.I 0.63 vitronectin precursor P04004
(VTNC_HUMAN) R.ERVYFFK.G 0.81 vitronectin precursor P04004
(VTNC_HUMAN) R.FEDGVLDPDYPR.N 0.64 vitronectin precursor P04004
(VTNC_HUMAN) R.IYISGM*APRPSLAK.K 0.75 zinc finger protein P52746
(ZN142_HUMAN) K.TRFLLR.T 0.66 142
TABLE-US-00010 TABLE 9 Significant peptides (AUC >0.6) for for
X!Tandem only Protein description Uniprot ID (name) Peptide XT_AUC
afamin precursor P43652 K.HELTDEELQSLFTNFANVVDK.C 0.65 (AFAM_HUMAN)
afamin precursor P43652 R.NPFVFAPTLLTVAVHFEEVAK.S 0.91 (AFAM_HUMAN)
alpha-1- P01011 K.ADLSGITGAR.N 0.67 antichymotrypsin (AACT_HUMAN)
precursor alpha-1- P01011 K.MEEVEAMLLPETLKR.W 0.60 antichymotrypsin
(AACT_HUMAN) precursor alpha-1- P01011 K.WEMPFDPQDTHQSR.F 0.64
antichymotrypsin (AACT_HUMAN) precursor alpha-1- P01011
R.LYGSEAFATDFQDSAAAK.K 0.62 antichymotrypsin (AACT_HUMAN) precursor
alpha-1B-glycoprotein P04217 K.HQFLLTGDTQGR.Y 0.72 precursor
(A1BG_HUMAN) alpha-1B-glycoprotein P04217 K.NGVAQEPVHLDSPAIK.H 0.63
precursor (A1BG_HUMAN) alpha-1B-glycoprotein P04217
K.SLPAPWLSM*APVSWITPGLK.T 0.72 precursor (A1BG_HUMAN)
alpha-1B-glycoprotein P04217 K.VTLTCVAPLSGVDFQLRR.G 0.67 precursor
(A1BG_HUMAN) alpha-1B-glycoprotein P04217 R.C*EGPIPDVTFELLR.E 0.67
precursor (A1BG_HUMAN) alpha-1B-glycoprotein P04217 R.C*LAPLEGAR.F
0.79 precursor (A1BG_HUMAN) alpha-1B-glycoprotein P04217
R.CLAPLEGAR.F 0.63 precursor (A1BG_HUMAN) alpha-1B-glycoprotein
P04217 R.GVTFLLR.R 0.69 precursor (A1BG_HUMAN)
alpha-1B-glycoprotein P04217 R.LHDNQNGWSGDSAPVELILSDETL 0.60
precursor (A1BG_HUMAN) PAPEFSPEPESGR.A alpha-1B-glycoprotein P04217
R.TPGAAANLELIFVGPQHAGNYR.C 0.62 precursor (A1BG_HUMAN)
alpha-2-antiplasmin P08697 K.HQM*DLVATLSQLGLQELFQAPDL 0.61 isoform
a precursor (A2AP_HUMAN) R.G alpha-2-antiplasmin P08697
R.LCQDLGPGAFR.L 0.68 isoform a precursor (A2AP_HUMAN)
alpha-2-antiplasmin P08697 R.WFLLEQPEIQVAHFPFK.N 0.60 isoform a
precursor (A2AP_HUMAN) alpha-2-HS- P02765
K.VWPQQPSGELFEIEIDTLETTCHVL 0.61 glycoprotein (FETUA_HUMAN)
DPTPVAR.C preproprotein alpha-2-HS- P02765 R.HTFMGVVSLGSPSGEVSHPR.K
0.68 glycoprotein (FETUA_HUMAN) preproprotein alpha-2-HS- P02765
R.Q*PNCDDPETEEAALVAIDYINQNL 0.69 glycoprotein (FETUA_HUMAN) PWGYK.H
preproprotein alpha-2-HS- P02765 R.QPNCDDPETEEAALVAIDYINQNLP 0.64
glycoprotein (FETUA_HUMAN) WGYK.H preproprotein alpha-2-HS- P02765
R.TVVQPSVGAAAGPVVPPCPGR.I 0.64 glycoprotein (FETUA_HUMAN)
preproprotein angiotensinogen P01019 K.QPFVQGLALYTPVVLPR.S 0.73
preproprotein (ANGT_HUMAN) angiotensinogen P01019
R.AAM*VGM*LANFLGFR.I 0.62 preproprotein (ANGT_HUMAN) apolipoprotein
A-IV P06727 K.LVPFATELHER.L 0.64 precursor (APOA4_HUMAN)
apolipoprotein A-IV P06727 R.LLPHANEVSQK.I 0.61 precursor
(APOA4_HUMAN) apolipoprotein A-IV P06727 R.SLAPYAQDTQEKLNHQLEGLTFQM
0.70 precursor (APOA4_HUMAN) K.K apolipoprotein B-100 P04114
K.FPEVDVLTK.Y 0.61 precursor (APOB_HUMAN) apolipoprotein B-100
P04114 K.HINIDQFVR.K 0.70 precursor (APOB_HUMAN) apolipoprotein
B-100 P04114 K.LLSGGNTLHLVSTTK.T 0.66 precursor (APOB_HUMAN)
apolipoprotein B-100 P04114 K.Q*VFLYPEKDEPTYILNIKR.G 0.81 precursor
(APOB_HUMAN) apolipoprotein B-100 P04114 K.QVFLYPEKDEPTYILNIKR.G
0.77 precursor (APOB_HUMAN) apolipoprotein B-100 P04114
K.SLHMYANR.L 0.83 precursor (APOB_HUMAN) apolipoprotein B-100
P04114 K.SVSDGIAALDLNAVANK.I 0.62 precursor (APOB_HUMAN)
apolipoprotein B-100 P04114 K.SVSLPSLDPASAKIEGNLIFDPNNYL 0.67
precursor (APOB_HUMAN) PK.E apolipoprotein B-100 P04114
K.TEVIPPLIENR.Q 0.63 precursor (APOB_HUMAN) apolipoprotein B-100
P04114 K.VLVDHFGYTK.D 0.76 precursor (APOB_HUMAN) apolipoprotein
B-100 P04114 R.TSSFALNLPTLPEVKFPEVDVLTK.Y 0.62 precursor
(APOB_HUMAN) apolipoprotein C-III P02656 R.GWVTDGFSSLKDYWSTVK.D
0.66 precursor (APOC3_HUMAN) apolipoprotein E P02649
R.GEVQAMLGQSTEELR.V 0.81 precursor (APOE_HUMAN) apolipoprotein E
P02649 R.LAVYQAGAR.E 0.63 precursor (APOE_HUMAN) apolipoprotein E
P02649 R.LGPLVEQGR.V 0.69 precursor (APOE_HUMAN) attractin isoform
2 O75882 K.LTLTPWVGLR.K 0.69 preproprotein (ATRN_HUMAN)
beta-2-glycoprotein 1 P02749 K.FICPLTGLWPINTLK.C 0.63 precursor
(APOH_HUMAN) beta-2-glycoprotein 1 P02749 K.TFYEPGEEITYSCKPGYVSR.G
0.62 precursor (APOH_HUMAN) beta-Ala-His Q96KN2
K.MVVSMTLGLHPWIANIDDTQYLA 0.81 dipeptidase precursor (CNDP1_HUMAN)
AK.R beta-Ala-His Q96KN2 K.VFQYIDLHQDEFVQTLK.E 0.65 dipeptidase
precursor (CNDP1_HUMAN) biotinidase precursor P43251
R.TSIYPFLDFM*PSPQVVR.W 0.79 (BTD_HUMAN) carboxypeptidase N P15169
R.ELMLQLSEFLCEEFR.N 0.61 catalytic chain (CBPN_HUMAN) precursor
ceruloplasmin P00450 K.AEEEHLGILGPQLHADVGDKVK.I 0.73 precursor
(CERU_HUMAN) ceruloplasmin P00450 K.ALYLQYTDETFR.T 0.64 precursor
(CERU_HUMAN) ceruloplasmin P00450 K.DVDKEFYLFPTVFDENESLLLEDNIR 0.62
precursor (CERU_HUMAN) .M ceruloplasmin P00450
K.HYYIGIIETTWDYASDHGEK.K 0.61 precursor (CERU_HUMAN) ceruloplasmin
P00450 R.EYTDASFTNRK.E 0.67 precursor (CERU_HUMAN) ceruloplasmin
P00450 R.HYYIAAEEIIWNYAPSGIDIFTK.E 0.63 precursor (CERU_HUMAN)
ceruloplasmin P00450 R.IYHSHIDAPK.D 0.62 precursor (CERU_HUMAN)
ceruloplasmin P00450 R.Q*KDVDKEFYLFPTVFDENESLLLE 0.74 precursor
(CERU_HUMAN) DNIR.M ceruloplasmin P00450
R.QKDVDKEFYLFPTVFDENESLLLED 0.65 precursor (CERU_HUMAN) NIR.M
ceruloplasmin P00450 R.TYYIAAVEVEWDYSPQR.E 0.90 precursor
(CERU_HUMAN) coagulation factor IX P00740 R.SALVLQYLR.V 0.69
preproprotein (FA9_HUMAN) coagulation factor V P12259
K.EFNPLVIVGLSK.D 0.61 precursor (FA5_HUMAN) coagulation factor XII
P00748 R.NPDNDIRPWCFVLNR.D 0.65 precursor (FA12_HUMAN) coagulation
factor XII P00748 R.VVGGLVALR.G 0.61 precursor (FA12_HUMAN)
complement C1q P02746 K.NSLLGMEGANSIFSGFLLFPDMEA.- 0.64
subcomponent subunit (C1QB_HUMAN) B precursor complement C1q P02746
K.VPGLYYFTYHASSR.G 0.63 subcomponent subunit (C1QB_HUMAN) B
precursor complement C1q P02747 R.Q*THQPPAPNSLIR.F 0.60
subcomponent subunit (C1QC_HUMAN) C precursor complement C1r P00736
R.LPVANPQACENWLR.G 0.72 subcomponent (C1R_HUMAN) precursor
complement C2 P06681 K.NQGILEFYGDDIALLK.L 0.74 isoform 3
(CO2_HUMAN) complement C2 P06681 K.RNDYLDIYAIGVGK.L 0.61 isoform 3
(CO2_HUMAN) complement C2 P06681 R.QPYSYDFPEDVAPALGTSFSHMLG 0.78
isoform 3 (CO2_HUMAN) ATNPTQK.T complement C3 P01024 R.IHWESASLLR.S
0.69 precursor (CO3_HUMAN) complement C4-A P0C0L4 K.FACYYPR.V 0.64
isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4
K.LHLETDSLALVALGALDTALYAAGS 0.74 isoform 1 (CO4A_HUMAN) K.S
complement C4-A P0C0L4 K.LVNGQSHISLSK.A 0.64 isoform 1 (CO4A_HUMAN)
complement C4-A P0C0L4 K.M*RPSTDTITVMVENSHGLR.V 0.60 isoform 1
(CO4A_HUMAN)
complement C4-A P0C0L4 K.MRPSTDTITVMVENSHGLR.V 0.65 isoform 1
(CO4A_HUMAN) complement C4-A P0C0L4 K.SCGLHQLLR.G 0.74 isoform 1
(CO4A_HUMAN) complement C4-A P0C0L4 K.VGLSGMAIADVTLLSGFHALR.A 0.61
isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4 K.YVLPNFEVK.I 0.64
isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4
R.ALEILQEEDLIDEDDIPVR.S 0.64 isoform 1 (CO4A_HUMAN) complement C4-A
P0C0L4 R.ECVGFEAVQEVPVGLVQPASATLY 0.62 isoform 1 (CO4A_HUMAN)
DYYNPER.R complement C4-A P0C0L4 R.EELVYELNPLDHR.G 0.66 isoform 1
(CO4A_HUMAN) complement C4-A P0C0L4 R.STQDTVIALDALSAYWIASHTTEER.G
0.70 isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4 R.VGDTLNLNLR.A
0.79 isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4 R.VHYTVCIWR.N
0.65 isoform 1 (CO4A_HUMAN) complement C4-B-like P0C0L5
K.GLCVATPVQLR.V 1.00 preproprotein (CO4B_HUMAN) complement
C4-B-like P0C0L5 K.KYVLPNFEVK.I 0.60 preproprotein (CO4B_HUMAN)
complement C4-B-like P0C0L5 K.VDFTLSSERDFALLSLQVPLKDAK.S 0.74
preproprotein (CO4B_HUMAN) complement C4-B-like P0C0L5
R.EMSGSPASGIPVK.V 0.72 preproprotein (CO4B_HUMAN) complement
C4-B-like P0C0L5 R.GCGEQTM*IYLAPTLAASR.Y 0.75 preproprotein
(CO4B_HUMAN) complement C4-B-like P0C0L5
R.NGESVKLHLETDSLALVALGALDTA 0.85 preproprotein (CO4B_HUMAN)
LYAAGSK.S complement C5 P01031 R.IPLDLVPK.T 0.65 preproprotein
(CO5_HUMAN) complement C5 P01031 R.SYFPESWLWEVHLVPR.R 0.63
preproprotein (CO5_HUMAN) complement C5 P01031
R.YGGGFYSTQDTINAIEGLTEYSLLVK 0.62 preproprotein (CO5_HUMAN) .Q
complement P13671 K.ENPAVIDFELAPIVDLVR.N 0.63 component C6
(CO6_HUMAN) precursor complement P07357 K.YNPVVIDFEMQPIHEVLR.H 0.61
component C8 alpha (CO8A_HUMAN) chain precursor complement P07357
R.HTSLGPLEAK.R 0.65 component C8 alpha (CO8A_HUMAN) chain precursor
complement P07358 K.C*QHEMDQYWGIGSLASGINLFTN 0.61 component C8 beta
(CO8B_HUMAN) SFEGPVLDHR.Y chain preproprotein complement P07358
K.SGFSFGFK.I 0.64 component C8 beta (CO8B_HUMAN) chain
preproprotein complement P07358 R.DTMVEDLVVLVR.G 0.77 component C8
beta (CO8B_HUMAN) chain preproprotein complement P07360
K.ANFDAQQFAGTWLLVAVGSACR.F 0.63 component C8 gamma (CO8G_HUMAN)
chain precursor complement P07360 R.AEATTLHVAPQGTAMAVSTFR.K 0.61
component C8 gamma (CO8G_HUMAN) chain precursor complement P02748
R.DVVLTTTFVDDIK.A 0.73 component C9 (CO9_HUMAN) precursor
complement P02748 R.RPWNVASLIYETK.G 0.66 component C9 (CO9_HUMAN)
precursor complement factor B P00751 K.ISVIRPSK.G 0.70
preproprotein (CFAB_HUMAN) complement factor B P00751 K.VASYGVKPR.Y
0.63 preproprotein (CFAB_HUMAN) complement factor B P00751
R.DFHINLFQVLPWLK.E 0.68 preproprotein (CFAB_HUMAN) complement
factor B P00751 R.DLLYIGK.D 0.63 preproprotein (CFAB_HUMAN)
complement factor B P00751 R.GDSGGPLIVHK.R 0.63 preproprotein
(CFAB_HUMAN) complement factor B P00751 R.LEDSVTYHCSR.G 0.68
preproprotein (CFAB_HUMAN) complement factor B P00751
R.LPPTTTCQQQK.E 0.68 preproprotein (CFAB_HUMAN) complement factor H
P08603 K.CLHPCVISR.E 0.62 isoform a precursor (CFAH_HUMAN)
complement factor H P08603 K.CTSTGWIPAPR.C 0.74 isoform a precursor
(CFAH_HUMAN) complement factor H P08603 K.IDVHLVPDR.K 0.66 isoform
a precursor (CFAH_HUMAN) complement factor H P08603
K.IVSSAMEPDREYHFGQAVR.F 0.67 isoform a precursor (CFAH_HUMAN)
complement factor H P08603 K.SIDVACHPGYALPK.A 0.67 isoform a
precursor (CFAH_HUMAN) complement factor H P08603
K.VSVLCQENYLIQEGEEITCKDGR.W 0.63 isoform a precursor (CFAH_HUMAN)
complement factor H P08603 K.WSSPPQCEGLPCK.S 0.60 isoform a
precursor (CFAH_HUMAN) complement factor H P08603 R.EIMENYNIALR.W
0.61 isoform a precursor (CFAH_HUMAN) complement factor H P08603
R.RPYFPVAVGK.Y 0.83 isoform a precursor (CFAH_HUMAN) complement
factor H P08603 R.WQSIPLCVEK.I 0.63 isoform a precursor
(CFAH_HUMAN) complement factor I P05156 R.YQIWTTVVDWIHPDLKR.I 0.72
preproprotein (CFAI_HUMAN) corticosteroid-binding P08185
K.AVLQLNEEGVDTAGSTGVTLNLTSK 0.61 globulin precursor (CBG_HUMAN)
PIILR.F corticosteroid-binding P08185 R.GLASANVDFAFSLYK.H 0.66
globulin precursor (CBG_HUMAN) fibrinogen alpha chain P02671
K.TFPGFFSPMLGEFVSETESR.G 0.62 isoform alpha-E (FIBA_HUMAN)
preproprotein gelsolin isoform b P06396
K.FDLVPVPTNLYGDFFTGDAYVILK.T 0.66 (GELS_HUMAN) gelsolin isoform b
P06396 K.QTQVSVLPEGGETPLFK.Q 0.66 (GELS_HUMAN) gelsolin isoform b
P06396 K.TPSAAYLWVGTGASEAEK.T 0.71 (GELS_HUMAN) gelsolin isoform b
P06396 R.AQPVQVAEGSEPDGFWEALGGK.A 0.67 (GELS_HUMAN) gelsolin
isoform b P06396 R.IEGSNKVPVDPATYGQFYGGDSYIIL 0.60 (GELS_HUMAN)
YNYR.H gelsolin isoform b P06396 R.VEKFDLVPVPTNLYGDFFTGDAYVI 0.73
(GELS_HUMAN) LK.T gelsolin isoform b P06396
R.VPFDAATLHTSTAMAAQHGMDD 0.63 (GELS_HUMAN) DGTGQK.Q glutathione
peroxidase P22352 K.FLVGPDGIPIMR.W 0.60 3 precursor (GPX3_HUMAN)
hemopexin precursor P02790 K.ALPQPQNVTSLLGCTH.- 0.63 (HEMO_HUMAN)
hemopexin precursor P02790 K.SLGPNSCSANGPGLYLIHGPNLYCY 0.68
(HEMO_HUMAN) SDVEK.L hemopexin precursor P02790
R.DGWHSWPIAHQWPQGPSAVDAA 0.63 (HEMO_HUMAN) FSWEEK.L hemopexin
precursor P02790 R.GECQAEGVLFFQGDR.E 0.67 (HEMO_HUMAN) hemopexin
precursor P02790 R.GECQAEGVLFFQGDREWFWDLAT 0.67 (HEMO_HUMAN)
GTM*K.E hemopexin precursor P02790 R.LEKEVGTPHGIILDSVDAAFICPGSS
0.75 (HEMO_HUMAN) R.L hemopexin precursor P02790 R.LWWLDLK.S 0.62
(HEMO_HUMAN) hemopexin precursor P02790 R.WKNFPSPVDAAFR.Q 0.68
(HEMO_HUMAN) heparin cofactor 2 P05546 K.DQVNTFDNIFIAPVGISTAMGMISL
0.60 precursor (HEP2_HUMAN) GLK.G insulin-like growth P35858
K.ANVFVQLPR.L 0.71 factor-binding protein (ALS_HUMAN) complex acid
labile subunit isoform 2 precursor insulin-like growth P35858
R.LEALPNSLLAPLGR.L 0.61 factor-binding protein (ALS_HUMAN) complex
acid labile subunit isoform 2 precursor insulin-like growth P35858
R.LFQGLGK.L 0.68 factor-binding protein (ALS_HUMAN) complex acid
labile subunit isoform 2 precursor insulin-like growth P35858
R.NLIAAVAPGAFLGLK.A 0.76 factor-binding protein (ALS_HUMAN) complex
acid labile subunit isoform 2 precursor insulin-like growth P35858
R.TFTPQPPGLER.L 0.73 factor-binding protein (ALS_HUMAN) complex
acid labile subunit isoform 2 precursor inter-alpha-trypsin P19827
K.Q*LVHHFEIDVDIFEPQGISK.L 0.69 inhibitor heavy chain (ITIH1_HUMAN)
H1 isoform a precursor inter-alpha-trypsin P19827 K.VTFQLTYEEVLK.R
0.61 inhibitor heavy chain (ITIH1_HUMAN) H1 isoform a precursor
inter-alpha-trypsin P19827 K.VTFQLTYEEVLKR.N 0.70
inhibitor heavy chain (ITIH1_HUMAN) H1 isoform a precursor
inter-alpha-trypsin P19827 R.GIEILNQVQESLPELSNHASILIMLT 0.62
inhibitor heavy chain (ITIH1_HUMAN) DGDPTEGVTDR.S H1 isoform a
precursor inter-alpha-trypsin P19827 R.GM*ADQDGLKPTIDKPSEDSPPLE
0.79 inhibitor heavy chain (ITIH1_HUMAN) M*LGPR.R H1 isoform a
precursor inter-alpha-trypsin P19827 R.KAAISGENAGLVR.A 0.78
inhibitor heavy chain (ITIH1_HUMAN) H1 isoform a precursor
inter-alpha-trypsin P19823 K.AGELEVFNGYFVHFFAPDNLDPIPK 0.64
inhibitor heavy chain (ITIH2_HUMAN) .N H2 precursor
inter-alpha-trypsin P19823 K.FYNQVSTPLLR.N 0.68 inhibitor heavy
chain (ITIH2_HUMAN) H2 precursor inter-alpha-trypsin P19823
K.VQFELHYQEVK.W 0.68 inhibitor heavy chain (ITIH2_HUMAN) H2
precursor inter-alpha-trypsin P19823 R.ETAVDGELVVLYDVK.R 0.63
inhibitor heavy chain (ITIH2_HUMAN) H2 precursor
inter-alpha-trypsin P19823 R.IYLQPGR.L 0.75 inhibitor heavy chain
(ITIH2_HUMAN) H2 precursor inter-alpha-trypsin Q06033
R.LWAYLTIEQLLEK.R 0.60 inhibitor heavy chain (ITIH3_HUMAN) H3
preproprotein inter-alpha-trypsin Q14624 K.ITFELVYEELLK.R 0.60
inhibitor heavy chain (ITIH4_HUMAN) H4 isoform 1 precursor
inter-alpha-trypsin Q14624 K.LQDRGPDVLTATVSGK.L 0.67 inhibitor
heavy chain (ITIH4_HUMAN) H4 isoform 1 precursor
inter-alpha-trypsin Q14624 K.TGLLLLSDPDKVTIGLLFWDGRGEG 0.63
inhibitor heavy chain (ITIH4_HUMAN) LR.L H4 isoform 1 precursor
inter-alpha-trypsin Q14624 K.WKETLFSVM*PGLK.M 0.79 inhibitor heavy
chain (ITIH4_HUMAN) H4 isoform 1 precursor inter-alpha-trypsin
Q14624 R.AISGGSIQIENGYFVHYFAPEGLTT 0.60 inhibitor heavy chain
(ITIH4_HUMAN) M*PK.N H4 isoform 1 precursor inter-alpha-trypsin
Q14624 R.AISGGSIQIENGYFVHYFAPEGLTT 0.65 inhibitor heavy chain
(ITIH4_HUMAN) MPK.N H4 isoform 1 precursor inter-alpha-trypsin
Q14624 R.ANTVQEATFQMELPK.K 0.68 inhibitor heavy chain (ITIH4_HUMAN)
H4 isoform 1 precursor inter-alpha-trypsin Q14624
R.SFAAGIQALGGTNINDAMLMAVQ 0.64 inhibitor heavy chain (ITIH4_HUMAN)
LLDSSNQEER.L H4 isoform 1 precursor inter-alpha-trypsin Q14624
R.VQGNDHSATR.E 0.63 inhibitor heavy chain (ITIH4_HUMAN) H4 isoform
1 precursor inter-alpha-trypsin Q14624 K.ITFELVYEELLKR.R 0.60
inhibitor heavy chain (ITIH4_HUMAN) H4 isoform 2 precursor
inter-alpha-trypsin Q14624 K.VTIGLLFWDGR.G 0.65 inhibitor heavy
chain (ITIH4_HUMAN) H4 isoform 2 precursor inter-alpha-trypsin
Q14624 R.LWAYLTIQQLLEQTVSASDADQQA 0.68 inhibitor heavy chain
(ITIH4_HUMAN) LR.N H4 isoform 2 precursor kallistatin precursor
P29622 K.LFHTNFYDTVGTIQLINDHVK.K 0.73 (KAIN_HUMAN) kininogen-1
isoform 2 P01042 K.ENFLFLTPDCK.S 0.64 precursor (KNG1_HUMAN)
kininogen-1 isoform 2 P01042 K.IYPTVNCQPLGMISLMK.R 0.64 precursor
(KNG1_HUMAN) kininogen-1 isoform 2 P01042 K.KIYPTVNCQPLGMISLMK.R
0.78 precursor (KNG1_HUMAN) kininogen-1 isoform 2 P01042
K.SLWNGDTGECTDNAYIDIQLR.I 0.67 precursor (KNG1_HUMAN) lumican
precursor P51884 K.ILGPLSYSK.I 0.60 (LUM_HUMAN) N-acetylmuramoyl-L-
Q96PD5 K.EYGVVLAPDGSTVAVEPLLAGLEAG 0.61 alanine amidase
(PGRP2_HUMAN) LQGR.R precursor N-acetylmuramoyl-L- Q96PD5
R.EGKEYGVVLAPDGSTVAVEPLLAGL 0.69 alanine amidase (PGRP2_HUMAN)
EAGLQGR.R precursor N-acetylmuramoyl-L- Q96PD5
R.Q*NGAALTSASILAQQVWGTLVLL 0.60 alanine amidase (PGRP2_HUMAN) QR.L
precursor pigment epithelium- P36955 K.IAQLPLTGSMSIIFFLPLK.V 0.65
derived factor (PEDF_HUMAN) precursor pigment epithelium- P36955
R.SSTSPTTNVLLSPLSVATALSALSLG 0.79 derived factor (PEDF_HUMAN)
AEQR.T precursor plasma kallikrein P03952 K.VAEYMDWILEK.T 0.62
preproprotein (KLKB1_HUMAN) plasma kallikrein P03952
R.C*LLFSFLPASSINDMEKR.F 0.60 preproprotein (KLKB1_HUMAN) plasma
kallikrein P03952 R.C*QFFSYATQTFHK.A 0.60 preproprotein
(KLKB1_HUMAN) plasma kallikrein P03952 R.CLLFSFLPASSINDMEK.R 0.76
preproprotein (KLKB1_HUMAN) plasma protease C1 P05155
R.LVLLNAIYLSAK.W 0.96 inhibitor precursor (IC1_HUMAN) pregnancy
zone protein P20742 R.NALFCLESAWNVAK.E 0.67 precursor (PZP_HUMAN)
pregnancy zone protein P20742 R.NQGNTWLTAFVLK.T 0.61 precursor
(PZP_HUMAN) pregnancy-specific Q00887 R.SNPVILNVLYGPDLPR.I 0.62
beta-1-glycoprotein 9 (PSG9_HUMAN) precursor prenylcysteine oxidase
Q9UHG3 K.IAIIGAGIGGTSAAYYLR.Q 0.71 1 precursor (PCYOX_HUMAN)
protein AMBP P02760 K.WYNLAIGSTCPWLK.K 0.77 preproprotein
(AMBP_HUMAN) protein AMBP P02760 R.TVAACNLPIVR.G 0.66 preproprotein
(AMBP_HUMAN) prothrombin P00734 R.IVEGSDAEIGMSPWQVMLFR.K 0.62
preproprotein (THRB_HUMAN) prothrombin P00734
R.RQECSIPVCGQDQVTVAMTPR.S 0.69 preproprotein (THRB_HUMAN)
prothrombin P00734 R.TFGSGEADCGLRPLFEK.K 0.61 preproprotein
(THRB_HUMAN) retinol-binding protein P02753 R.FSGTWYAMAK.K 0.60 4
precursor (RET4_HUMAN) retinol-binding protein P02753
R.LLNNWDVCADMVGTFTDTEDPAK 0.64 4 precursor (RET4_HUMAN) .F serum
amyloid P- P02743 R.GYVIIKPLVWV.- 0.62 component precursor
(SAMP_HUMAN) sex hormone-binding P04278
K.VVLSSGSGPGLDLPLVLGLPLQLK.L 0.60 globulin isoform 1 (SHBG_HUMAN)
precursor sex hormone-binding P04278 R.TWDPEGVIFYGDTNPKDDWFM*L 0.75
globulin isoform 1 (SHBG_HUMAN) GLR.D precursor sex hormone-binding
P04278 R.TWDPEGVIFYGDTNPKDDWFMLG 0.74 globulin isoform 1
(SHBG_HUMAN) LR.D precursor thrombospondin-1 P07996 K.GFLLLASLR.Q
0.70 precursor (TSP1_HUMAN) thyroxine-binding P05543 K.AVLHIGEK.G
0.85 globulin precursor (THBG_HUMAN) thyroxine-binding P05543
K.FSISATYDLGATLLK.M 0.65 globulin precursor (THBG_HUMAN)
thyroxine-binding P05543 K.KELELQIGNALFIGK.H 0.61 globulin
precursor (THBG_HUMAN) thyroxine-binding P05543 K.MSSINADFAFNLYR.R
0.67 globulin precursor (THBG_HUMAN) transforming growth Q15582
R.LTLLAPLNSVFK.D 0.65 factor-beta-induced (BGH3_HUMAN) protein
ig-h3 precursor transthyretin precursor P02766 R.GSPAINVAVHVFR.K
0.67 (TTHY_HUMAN) uncharacterized Q8ND61 K.MPSHLMLAR.K 0.64 protein
C3orf20 (CC020_HUMAN) isoform 1 vitamin D-binding P02774
K.ELPEHTVK.L 0.75 protein isoform 1 (VTDB_HUMAN) precursor vitamin
D-binding P02774 K.EYANQFMWEYSTNYGQAPLSLLVS 0.69 protein isoform 1
(VTDB_HUMAN) YTK.S precursor vitamin D-binding P02774
K.HLSLLTTLSNR.V 0.65 protein isoform 1 (VTDB_HUMAN) precursor
vitamin D-binding P02774 K.HQPQEFPTYVEPTNDEICEAFR.K 0.64 protein
isoform 1 (VTDB_HUMAN) precursor vitamin D-binding P02774
K.LAQKVPTADLEDVLPLAEDITNILSK.C 0.73 protein isoform 1 (VTDB_HUMAN)
precursor vitamin D-binding P02774 K.LCDNLSTK.N 0.70 protein
isoform 1 (VTDB_HUMAN) precursor vitamin D-binding P02774
K.LCMAALK.H 0.63 protein isoform 1 (VTDB_HUMAN) precursor vitamin
D-binding P02774 K.SCESNSPFPVHPGTAECCTK.E 0.63 protein isoform 1
(VTDB_HUMAN) precursor vitamin D-binding P02774
K.SYLSMVGSCCTSASPTVCFLK.E 0.61 protein isoform 1 (VTDB_HUMAN)
precursor
vitamin D-binding P02774 K.TAMDVFVCTYFM*PAAQLPELPDV 0.61 protein
isoform 1 (VTDB_HUMAN) ELPTNK.D precursor vitamin D-binding P02774
K.VLEPTLK.S 0.69 protein isoform 1 (VTDB_HUMAN) precursor vitamin
D-binding P02774 R.KFPSGTFEQVSQLVK.E 0.66 protein isoform 1
(VTDB_HUMAN) precursor vitamin D-binding P02774 R.THLPEVFLSK.V 0.62
protein isoform 1 (VTDB_HUMAN) precursor vitamin D-binding P02774
R.TSALSAK.S 0.74 protein isoform 1 (VTDB_HUMAN) precursor
vitronectin precursor P04004 R.GQYCYELDEK.A 0.73 (VTNC_HUMAN)
vitronectin precursor P04004 R.M*DWLVPATCEPIQSVFFFSGDK.Y 0.64
(VTNC_HUMAN) vitronectin precursor P04004 R.Q*PQFISR.D 0.63
(VTNC_HUMAN)
TABLE-US-00011 TABLE 10 Significant peptides (AUC >0.6) for both
X!Tandem and Sequest Protein description Uniprot ID (name) Peptide
XT_AUC S_AUC afamin precursor P43652 K.HFQNLGK.D 0.74 0.61
(AFAM_HUMAN) afamin precursor P43652 R.RHPDLSIPELL 0.67 0.63
(AFAM_HUMAN) R.I afamin precursor P43652 R.TINPAVDHCC 0.66 0.86
(AFAM_HUMAN) K.T alpha-1-antichymotrypsin P01011 K.ITDLIKDLDSQ 0.71
0.73 precursor (AACT_HUMAN) TMMVLVNYIFF K.A
alpha-1-antichymotrypsin P01011 R.DYNLNDILLQ 0.74 0.62 precursor
(AACT_HUMAN) LGIEEAFTSK.A alpha-1-antichymotrypsin P01011
R.GTHVDLGLAS 0.76 0.61 precursor (AACT_HUMAN) ANVDFAFSLYK.Q
alpha-1B-glycoprotein P04217 K.SLPAPWLSMA 0.71 0.65 precursor
(A1BG_HUMAN) PVSWITPGLK.T alpha-2-antiplasmin P08697 K.GFPIKEDFLEQ
0.66 0.69 isoform a precursor (A2AP_HUMAN) SEQLFGAKPVSL TGK.Q
alpha-2-antiplasmin P08697 K.HQMDLVATL 0.67 0.60 isoform a
precursor (A2AP_HUMAN) SQLGLQELFQAP DLR.G alpha-2-antiplasmin
P08697 R.QLTSGPNQEQ 0.66 0.61 isoform a precursor (A2AP_HUMAN)
VSPLTLLK.L alpha-2-HS-glycoprotein P02765 R.AQLVPLPPST 0.64 0.63
preproprotein (FETUA_HUMAN) YVEFTVSGTDC VAK.E angiotensinogen
P01019 K.DPTFIPAPIQA 0.69 0.69 preproprotein (ANGT_HUMAN) K.T
angiotensinogen P01019 R.FM*QAVTGW 0.65 0.65 preproprotein
(ANGT_HUMAN) K.T antithrombin-III P01008 K.ANRPFLVFIR.E 0.72 0.60
precursor (ANT3_HUMAN) antithrombin-III P01008 K.GDDITMVLIL 0.69
0.68 precursor (ANT3_HUMAN) PKPEK.S antithrombin-III P01008
R.DIPMNPMCIY 0.63 0.78 precursor (ANT3_HUMAN) R.S apolipoprotein
A-IV P06727 K.KLVPFATELH 0.65 0.77 precursor (APOA4_HUMAN) ER.L
apolipoprotein A-IV P06727 K.SLAELGGHLD 0.60 0.75 precursor
(APOA4_HUMAN) QQVEEFR.R apolipoprotein B-100 P04114 K.ALYWVNGQV
0.61 0.63 precursor (APOB_HUMAN) PDGVSK.V apolipoprotein B-100
P04114 K.FIIPGLK.L 0.64 0.68 precursor (APOB_HUMAN) apolipoprotein
B-100 P04114 K.FSVPAGIVIPS 0.63 0.63 precursor (APOB_HUMAN)
FQALTAR.F apolipoprotein B-100 P04114 K.IEGNLIFDPNN 0.63 0.65
precursor (APOB_HUMAN) YLPK.E apolipoprotein B-100 P04114
K.LNDLNSVLV 0.91 0.88 precursor (APOB_HUMAN) MPTFHVPFTDL QVPSCK.L
apolipoprotein B-100 P04114 K.VELEVPQLCS 0.60 0.61 precursor
(APOB_HUMAN) FILK.T apolipoprotein B-100 P04114 K.VNWEEEAAS 0.60
0.73 precursor (APOB_HUMAN) GLLTSLK.D apolipoprotein B-100 P04114
R.ATLYALSHAV 0.78 0.80 precursor (APOB_HUMAN) NNYHK.T
apolipoprotein B-100 P04114 R.TGISPLALIK.G 0.64 0.77 precursor
(APOB_HUMAN) apolipoprotein B-100 P04114 R.TLQGIPQMIG 0.65 0.66
precursor (APOB_HUMAN) EVIR.K apolipoprotein C-III P02656
K.DALSSVQESQ 0.80 0.69 precursor (APOC3_HUMAN) VAQQAR.G
apolipoprotein C-IV P55056 R.DGWQWFWSP 0.63 0.67 precursor
(APOC4_HUMAN) STFR.G apolipoprotein E P02649 K.VQAAVGTSA 0.70 0.72
precursor (APOE_HUMAN) APVPSDNH.- apolipoprotein E P02649
R.WELALGR.F 0.88 0.60 precursor (APOE_HUMAN) beta-2-microglobulin
P61769 K.SNFLNCYVSG 0.60 0.70 precursor (B2MG_HUMAN) FHPSDIEVDLLK.N
bone marrow P13727 R.GGHCVALCT 0.83 0.86 proteoglycan isoform 1
(PRG2_HUMAN) R.G preproprotein carboxypeptidase B2 Q96IY4
R.LVDFYVMPV 0.61 0.65 preproprotein (CBPB2_HUMAN) VNVDGYDYSW K.K
carboxypeptidase B2 Q96IY4 R.YTHGHGSETL 0.60 0.68 preproprotein
(CBPB2_HUMAN) YLAPGGGDDWI YDLGIK.Y carboxypeptidase N P22792
K.LSNNALSGLP 0.65 0.67 subunit 2 precursor (CPN2_HUMAN) QGVFGK.L
carboxypeptidase N P22792 K.TLNLAQNLLA 0.67 0.69 subunit 2
precursor (CPN2_HUMAN) QLPEELFHPLTS LQTLK.L carboxypeptidase N
P22792 R.WLNVQLSPR.Q 0.74 0.67 subunit 2 precursor (CPN2_HUMAN)
ceruloplasmin precursor P00450 K.GDSVVWYLF 0.90 0.72 (CERU_HUMAN)
SAGNEADVHGI YFSGNTYLWR.G ceruloplasmin precursor P00450 K.MYYSAVDPT
0.70 0.82 (CERU_HUMAN) K.D ceruloplasmin precursor P00450
R.GPEEEHLGIL 0.60 0.65 (CERU_HUMAN) GPVIWAEVGDTI R.V ceruloplasmin
precursor P00450 R.IDTINLFPATL 0.66 0.70 (CERU_HUMAN) FDAYMVAQNP
GEWMLSCQNL NHLK.A ceruloplasmin precursor P00450 R.SGAGTEDSAC 0.88
0.92 (CERU_HUMAN) IPWAYYSTVDQ VKDLYSGLIGPL IVCR.R cholinesterase
precursor P06276 K.IFFPGVSEFGK 0.70 0.63 (CHLE_HUMAN) .E
cholinesterase precursor P06276 R.AILQSGSFNAP 0.75 0.77
(CHLE_HUMAN) WAVTSLYEAR.N chorionic gonadotropin, P01233
R.VLQGVLPALP 0.60 0.75 beta polypeptide 8 (CGHB_HUMAN) QVVCNYR.D
precursor chorionic P01243 R.ISLLLIESWLE 0.83 0.63
somatomammotropin (CSH_HUMAN) PVR.F hormone 2 isoform 2 precursor
coagulation factor XII P00748 R.LHEAFSPVSY 0.60 0.66 precursor
(FA12_HUMAN) QHDLALLR.L coagulation factor XII P00748 R.TTLSGAPCQP
0.69 0.82 precursor (FA12_HUMAN) WASEATYR.N complement C1q P02745
K.GLFQVVSGG 0.65 0.60 subcomponent subunit A (C1QA_HUMAN)
MVLQLQQGDQ precursor VWVEKDPK.K complement C1r P00736 K.VLNYVDWIK
0.80 0.76 subcomponent precursor (C1R_HUMAN) K.E complement C1s
P09871 K.SNALDIIFQTD 0.62 0.77 subcomponent precursor (C1S_HUMAN)
LTGQK.K complement C4-A P0C0L4 K.EGAIHREELV 0.76 0.75 isoform 1
(CO4A_HUMAN) YELNPLDHR.G complement C4-A P0C0L4 K.ITQVLHFTK.D 0.63
0.62 isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4 K.SHALQLNNR.Q
0.66 0.71 isoform 1 (CO4A_HUMAN) complement C4-A P0C0L4
R.AVGSGATFSH 0.65 0.60 isoform 1 (CO4A_HUMAN) YYYM*ILSR.G
complement C4-A P0C0L4 R.EPFLSCCQFA 0.64 0.72 isoform 1
(CO4A_HUMAN) ESLR.K complement C4-A P0C0L4 R.GHLFLQTDQP 0.63 0.76
isoform 1 (CO4A_HUMAN) IYNPGQR.V complement C4-A P0C0L4
R.GLEEELQFSL 0.68 0.68 isoform 1 (CO4A_HUMAN) GSK.I complement C4-A
P0C0L4 R.GSFEFPVGDA 0.67 0.70 isoform 1 (CO4A_HUMAN) VSK.V
complement C4-A P0C0L4 R.LLATLCSAEV 0.61 0.71 isoform 1
(CO4A_HUMAN) CQCAEGK.C complement C4-A P0C0L4 R.VQQPDCREPF 0.65
0.83 isoform 1 (CO4A_HUMAN) LSCCQFAESLRK .K complement C4-A P0C0L4
R.YIYGKPVQGV 0.82 0.76 isoform 1 (CO4A_HUMAN) AYVR.F complement C5
P01031 K.ITHYNYLILSK 0.66 0.69 preproprotein (CO5_HUMAN) .G
complement C5 P01031 R.ENSLYLTAFT 0.60 0.68 preproprotein
(CO5_HUMAN) VIGIR.K complement C5 P01031 R.KAFDICPLVK.I 0.77 0.65
preproprotein (CO5_HUMAN) complement C5 P01031 R.VDDGVASFVL 0.68
0.61 preproprotein (CO5_HUMAN) NLPSGVTVLEFN VK.T complement
component P13671 K.TFSEWLESVK 0.94 0.64 C6 precursor (CO6_HUMAN)
ENPAVIDFELAP IVDLVR.N complement component P13671 R.IFDDFGTHYF 0.78
0.75 C6 precursor (CO6_HUMAN) TSGSLGGVYDL LYQFSSEELK.N complement
component P10643 K.ELSHLPSLYD 0.69 0.71 C7 precursor (CO7_HUMAN)
YSAYR.R complement component P10643 R.RYSAWAESV 0.71 0.70 C7
precursor (CO7_HUMAN) TNLPQVIK.Q complement component P07357
K.YNPVVIDFEM 0.68 0.73 C8 alpha chain precursor (CO8A_HUMAN)
*QPIHEVLR.H complement component P07358 K.VEPLYELVTA 0.69 0.70 C8
beta chain (CO8B_HUMAN) TDFAYSSTVR.Q preproprotein
complement component P07358 R.SLM*LHYEFL 0.61 0.65 C8 beta chain
(CO8B_HUMAN) QR.V preproprotein complement component P07360
K.YGFCEAADQF 0.78 0.76 C8 gamma chain (CO8G_HUMAN) HVLDEVRR.-
precursor complement component P07360 R.FLQEQGHR.A 0.63 0.69 C8
gamma chain (CO8G_HUMAN) precursor complement component P07360
R.KLDGICWQV 0.75 0.70 C8 gamma chain (CO8G_HUMAN) R.Q precursor
complement component P07360 R.SLPVSDSVLS 0.70 0.60 C8 gamma chain
(CO8G_HUMAN) GFEQR.V precursor complement component P02748
R.GTVIDVTDFV 0.68 0.69 C9 precursor (CO9_HUMAN) NWASSINDAPV LISQK.L
complement factor B P00751 K.NPREDYLDV 0.72 0.77 preproprotein
(CFAB_HUMAN) YVFGVGPLVNQ VNINALASK.K complement factor B P00751
R.GDSGGPLIVH 0.60 0.76 preproprotein (CFAB_HUMAN) KR.S complement
factor B P00751 R.HVIILMTDGL 0.60 0.64 preproprotein (CFAB_HUMAN)
HNM*GGDPITVI DEIR.D complement factor B P00751 R.KNPREDYLDV 0.63
0.63 preproprotein (CFAB_HUMAN) YVFGVGPLVNQ VNINALASK.K complement
factor H P08603 K.SCDIPVFMNA 0.62 0.71 isoform a precursor
(CFAH_HUMAN) R.T complement factor H P08603 K.SPPEISHGVV 0.88 0.88
isoform a precursor (CFAH_HUMAN) AHMSDSYQYGE EVTYK.C complement
factor H P08603 K.TDCLSLPSFE 0.61 0.66 isoform a precursor
(CFAH_HUMAN) NAIPMGEKK.D complement factor I P05156 K.RAQLGDLPW
0.71 0.74 preproprotein (CFAI_HUMAN) QVAIK.D complement factor I
P05156 K.SLECLHPGTK.F 0.64 0.81 preproprotein (CFAI_HUMAN)
complement factor I P05156 R.TMGYQDFAD 0.73 0.75 preproprotein
(CFAI_HUMAN) VVCYTQK.A extracellular matrix Q16610 R.ELLALIQLER.E
0.69 0.65 protein 1 isoform 3 (ECM1_HUMAN) precursor gelsolin
isoform a P06396 R.VPEARPNSMV 0.76 0.62 precursor (GELS_HUMAN)
VEHPEFLK.A glutathione peroxidase 3 P22352 R.LFWEPMK.V 0.69 0.67
precursor (GPX3_HUMAN) hemopexin precursor P02790 R.DVRDYFMPCP 0.70
0.72 (HEMO_HUMAN) GR.G heparin cofactor 2 P05546 K.DALENIDPAT 0.61
0.65 precursor (HEP2_HUMAN) QMMILNCIYFK.G heparin cofactor 2 P05546
K.GLIKDALENI 0.64 0.64 precursor (HEP2_HUMAN) DPATQMMILNC IYFK.G
heparin cofactor 2 P05546 K.QFPILLDFK.T 0.61 0.69 precursor
(HEP2_HUMAN) heparin cofactor 2 P05546 R.VLKDQVNTF 0.88 0.75
precursor (HEP2_HUMAN) DNIFIAPVGISTA MGMISLGLK.G insulin-like
growth P35858 R.AFWLDVSHN 0.61 0.82 factor-binding protein
(ALS_HUMAN) R.L complex acid labile subunit isoform 2 precursor
inter-alpha-trypsin P19827 K.ADVQAHGEG 0.61 0.74 inhibitor heavy
chain H1 (ITIH1_HUMAN) QEFSITCLVDEE isoform a precursor EMKK.L
inter-alpha-trypsin P19827 K.ILGDM*QPGD 0.71 0.63 inhibitor heavy
chain H1 (ITIH1_HUMAN) YFDLVLFGTR.V isoform a precursor
inter-alpha-trypsin P19827 K.ILGDMQPGDY 0.68 0.60 inhibitor heavy
chain H1 (ITIH1_HUMAN) FDLVLFGTR.V isoform a precursor
inter-alpha-trypsin P19827 K.NVVFVIDISGS 0.76 0.83 inhibitor heavy
chain H1 (ITIH1_HUMAN) MR.G isoform a precursor inter-alpha-trypsin
P19827 K.TAFISDFAVT 0.74 0.63 inhibitor heavy chain H1
(ITIH1_HUMAN) ADGNAFIGDIKD isoform a precursor K.V
inter-alpha-trypsin P19827 R.GHMLENHVE 0.78 0.80 inhibitor heavy
chain H1 (ITIH1_HUMAN) R.L isoform a precursor inter-alpha-trypsin
P19827 R.GM*ADQDGL 0.61 0.62 inhibitor heavy chain H1 (ITIH1_HUMAN)
KPTIDKPSEDSP isoform a precursor PLEMLGPR.R inter-alpha-trypsin
P19827 R.LWAYLTIQEL 0.68 0.62 inhibitor heavy chain H1
(ITIH1_HUMAN) LAK.R isoform a precursor inter-alpha-trypsin P19827
R.NHM*QYEIVI 0.67 0.65 inhibitor heavy chain H1 (ITIH1_HUMAN) K.V
isoform a precursor inter-alpha-trypsin P19823 K.AHVSFKPTVA 0.75
0.61 inhibitor heavy chain H2 (ITIH2_HUMAN) QQR.I precursor
inter-alpha-trypsin P19823 K.ENIQDNISLFS 0.80 0.93 inhibitor heavy
chain H2 (ITIH2_HUMAN) LGM*GFDVDYD precursor FLKR.L
inter-alpha-trypsin P19823 K.ENIQDNISLFS 0.63 0.80 inhibitor heavy
chain H2 (ITIH2_HUMAN) LGMGFDVDYDF precursor LKR.L
inter-alpha-trypsin P19823 K.HLEVDVWVIE 0.61 0.61 inhibitor heavy
chain H2 (ITIH2_HUMAN) PQGLR.F precursor inter-alpha-trypsin P19823
K.LWAYLTINQL 0.69 0.62 inhibitor heavy chain H2 (ITIH2_HUMAN)
LAER.S precursor inter-alpha-trypsin P19823 R.AEDHFSVIDF 0.65 0.63
inhibitor heavy chain H2 (ITIH2_HUMAN) NQNIR.T precursor
inter-alpha-trypsin P19823 R.FLHVPDTFEG 0.66 0.62 inhibitor heavy
chain H2 (ITIH2_HUMAN) HFDGVPVISK.G precursor inter-alpha-trypsin
Q14624 K.ILDDLSPR.D 0.67 0.65 inhibitor heavy chain H4
(ITIH4_HUMAN) isoform 1 precursor inter-alpha-trypsin Q14624
K.IPKPEASFSPR.R 0.69 0.77 inhibitor heavy chain H4 (ITIH4_HUMAN)
isoform 1 precursor inter-alpha-trypsin Q14624 K.SPEQQETVLD 0.63
0.69 inhibitor heavy chain H4 (ITIH4_HUMAN) GNLIIR.Y isoform 1
precursor inter-alpha-trypsin Q14624 K.YIFHNFMER.L 0.66 0.61
inhibitor heavy chain H4 (ITIH4_HUMAN) isoform 1 precursor
inter-alpha-trypsin Q14624 R.FSSHVGGTLG 0.69 0.71 inhibitor heavy
chain H4 (ITIH4_HUMAN) QFYQEVLWGSP isoform 1 precursor AASDDGRR.T
inter-alpha-trypsin Q14624 R.GPDVLTATVS 0.63 0.82 inhibitor heavy
chain H4 (ITIH4_HUMAN) GK.L isoform 1 precursor inter-alpha-trypsin
Q14624 R.NMEQFQVSVS 0.78 0.60 inhibitor heavy chain H4
(ITIH4_HUMAN) VAPNAK.I isoform 1 precursor inter-alpha-trypsin
Q14624 R.RLDYQEGPPG 0.68 0.62 inhibitor heavy chain H4
(ITIH4_HUMAN) VEISCWSVEL.- isoform 1 precursor kallistatin
precursor P29622 K.IVDLVSELKK.D 0.75 0.67 (KAIN_HUMAN) kallistatin
precursor P29622 R.VGSALFLSHN 0.70 0.74 (KAIN_HUMAN) LK.F
kininogen-1 isoform 2 P01042 K.IYPTVNCQPL 0.89 0.62 precursor
(KNG1_HUMAN) GM*ISLM*K.R kininogen-1 isoform 2 P01042 K.TVGSDTFYSF
0.61 0.68 precursor (KNG1_HUMAN) K.Y kininogen-1 isoform 2 P01042
R.DIPTNSPELEE 0.61 0.76 precursor (KNG1_HUMAN) TLTHTITK.L
kininogen-1 isoform 2 P01042 R.VQVVAGK.K 0.67 0.71 precursor
(KNG1_HUMAN) lumican precursor P51884 R.FNALQYLR.L 0.68 0.76
(LUM_HUMAN) macrophage colony- P09603 K.VIPGPPALTLV 0.68 0.60
stimulating factor 1 (CSF1_HUMAN) PAELVR.I receptor precursor
monocyte differentiation P08571 K.ITGTMPPLPLE 0.80 0.67 antigen
CD14 precursor (CD14_HUMAN) ATGLALSSLR.L N-acetylmuramoyl-L- Q96PD5
K.EFTEAFLGCP 0.62 0.64 alanine amidase (PGRP2_HUMAN) AIHPR.C
precursor N-acetylmuramoyl-L- Q96PD5 R.RVINLPLDSM 0.63 0.62 alanine
amidase (PGRP2_HUMAN) AAPWETGDTFP precursor DVVAIAPDVR.A
phosphatidylinositol- P80108 R.GVFFSVNSWT 0.67 0.78 glycan-specific
(PHLD_HUMAN) PDSMSFIYK.A phospholipase D precursor pigment
epithelium- P36955 K.EIPDEISILLLGVAHF 0.63 0.61 derived factor
precursor (PEDF_HUMAN) K.G pigment epithelium- P36955
K.IAQLPLTGSM*SIIF 0.79 0.61 derived factor precursor (PEDF_HUMAN)
FLPLK.V pigment epithelium- P36955 K.TVQAVLTVPK.L 0.75 0.79 derived
factor precursor (PEDF_HUMAN) pigment epithelium- P36955
R.ALYYDLISSPDIHGT 0.60 0.73 derived factor precursor (PEDF_HUMAN)
YKELLDTVTAPQK.N pigment epithelium- P36955 R.DTDTGALLFIGK.I 0.85
0.62 derived factor precursor (PEDF_HUMAN) plasminogen isoform 1
P00747 R.ELRPWCFTTDPNK 0.70 0.68 precursor (PLMN_HUMAN) R.W
plasminogen isoform 1 P00747 R.TECFITGWGETQGT 0.63 0.68 precursor
(PLMN_HUMAN) FGAGLLK.E platelet basic protein P02775
K.GTHCNQVEVIATLK 0.60 0.61
preproprotein (CXCL7_HUMAN) .D pregnancy zone protein P20742
K.AVGYLITGYQR.Q 0.87 0.73 precursor (PZP_HUMAN) pregnancy zone
protein P20742 R.AVDQSVLLM*KPE 0.64 0.62 precursor (PZP_HUMAN)
AELSVSSVYNLLTVK.D pregnancy zone protein P20742 R.IQHPFTVEEFVLPK.F
0.66 0.74 precursor (PZP_HUMAN) pregnancy zone protein P20742
R.NELIPLIYLENPR.R 0.61 0.61 precursor (PZP_HUMAN) protein AMBP
P02760 R.AFIQLWAFDAVK.G 0.72 0.67 preproprotein (AMBP_HUMAN)
proteoglycan 4 isoform B Q92954 K.GFGGLTGQIVAALS 0.70 0.72
precursor (PRG4_HUMAN) TAK.Y prothrombin preproprotein P00734
K.YGFYTHVFR.L 0.70 0.63 (THRB_HUMAN) prothrombin preproprotein
P00734 R.IVEGSDAEIGM*SP 0.63 0.71 (THRB_HUMAN) WQVMLFR.K
retinol-binding protein 4 P02753 K.KDPEGLFLQDNIVA 0.67 0.67
precursor (RET4_HUMAN) EFSVDETGQMSATAK .G thyroxine-binding
globulin P05543 K.AQWANPFDPSKTE 0.67 0.80 precursor (THBG_HUMAN)
DSSSFLIDK.T thyroxine-binding globulin P05543 K.GWVDLFVPK.F 0.67
0.64 precursor (THBG_HUMAN) thyroxine-binding globulin P05543
R.SFM*LLILER.S 0.65 0.68 precursor (THBG_HUMAN) thyroxine-binding
globulin P05543 R.SFMLLILER.S 0.64 0.62 precursor (THBG_HUMAN)
vitamin D-binding protein P02774 K.EFSHLGKEDFTSLSL 0.74 0.61
isoform 1 precursor (VTDB_HUMAN) VLYSR.K vitamin D-binding protein
P02774 K.EYANQFM*WEYST 0.73 0.61 isoform 1 precursor (VTDB_HUMAN)
NYGQAPLSLLVSYTK.S vitamin D-binding protein P02774 K.HQPQEFPTYVEPTN
0.67 0.69 isoform 1 precursor (VTDB_HUMAN) DEICEAFRK.D vitamin
D-binding protein P02774 K.SYLSM*VGSCCTSA 0.63 0.62 isoform 1
precursor (VTDB_HUMAN) SPTVCFLK.E vitamin D-binding protein P02774
K.TAM*DVFVCTYFM 0.63 0.60 isoform 1 precursor (VTDB_HUMAN)
PAAQLPELPDVELPT NK.D vitamin D-binding protein P02774
K.VPTADLEDVLPLAE 0.70 0.71 isoform 1 precursor (VTDB_HUMAN)
DITNILSK.C vitronectin precursor P04004 K.AVRPGYPK.L 0.68 0.77
(VTNC_HUMAN) vitronectin precursor P04004 R.MDWLVPATCEPIQ 0.67 0.65
(VTNC_HUMAN) SVFFFSGDK.Y zinc-alpha-2-glycoprotein P25311
K.EIPAWVPFDPAAQI 0.63 0.67 precursor (ZA2G_HUMAN) TK.Q
[0178] The differentially expressed proteins identified by the
hypothesis-independent strategy above, not already present in our
MRM-MS assay, were candidates for incorporation into the MRM-MS
assay. Two additional proteins (AFP, PGH1) of functional interest
were also selected for MRM development. Candidates were prioritized
by AUC and biological function, with preference give for new
pathways. Sequences for each protein of interest, were imported
into Skyline software which generated a list of tryptic peptides,
m/z values for the parent ions and fragment ions, and an
instrument-specific collision energy (McLean et al. Bioinformatics
(2010) 26 (7): 966-968; McLean et al. Anal. Chem (2010) 82 (24):
10116-10124).
[0179] The list was refined by eliminating peptides containing
cysteines and methionies, and by using the shotgun data to select
the charge state(s) and a subset of potential fragment ions for
each peptide that had already been observed on a mass
spectrometer.
[0180] After prioritizing parent and fragment ions, a list of
transitions was exported with a single predicted collision energy.
Approximately 100 transitions were added to a single MRM run. For
development, MRM data was collected on either a QTRAP 5500 (AB
Sciex) or a 6490 QQQ (Agilent). Commercially available human female
serum (from pregnant and non-pregnant donors), was depleted and
processed to tryptic peptides, as described above, and used to
"scan" for peptides of interest. In some cases, purified synthetic
peptides were used for further optimization. For development,
digested serum or purified synthetic peptides were separated with a
15 min acetonitrile gradient at 100 ul/min on a 2.1.times.50 mM
Poroshell 120 EC-C18 column (Agilent) at 40.degree. C.
[0181] The MS/MS data was imported back into Skyline, where all
chromatograms for each peptide were overlayed and used to identify
a concensus peak corresponding to the peptide of interest and the
transitions with the highest intensities and the least noise. Table
11, contains a list of the most intensely observed candidate
transitions and peptides for transfer to the MRM assay.
TABLE-US-00012 TABLE 11 Candidate peptides and transitions for
transferring to the MRM assay fragment ion, m/z, Protein Peptide
m/z, charge charge, rank area alpha-1-antichymotrypsin
K.ADLSGITGAR.N 480.7591++ S [y7] - 661.3628+[1] 1437602 G [y6] -
574.3307+[2] 637584 T [y4] - 404.2252+[3] 350392 L [y8] -
774.4468+[4] 191870 G [y3] - 303.1775+[5] 150575 I [y5] -
517.3093+[6] 97828 alpha-1-antichymotrypsin K.EQLSLLDR.F 487.2693++
S [y5] - 603.3461+[1] 345602 L [y6] - 716.4301+[2] 230046 L [y4] -
516.3140+[3] 143874 D [y2] - 290.1459+[4] 113381 D [y2] -
290.1459+[5] 113381 Q [b2] - 258.1084+[6] 78157
alpha-1-antichymotrypsin K.ITLLSALVETR.T 608.3690++ S [y7] -
775.4308+[1] 1059034 L [y8] - 888.5149+[2] 541969 T [b2] -
215.1390+[3] 408819 L [y9] - 1001.5990+[4] 438441 V [y4] -
504.2776+[5] 311293 L [y5] - 617.3617+[6] 262544 L [b3] -
328.2231+[7] 197526 T [y2] - 276.1666+[8] 212816 E [y3] -
405.2092+[9] 207163 alpha-1-antichymotrypsin R.EIGELYLPK.F
531.2975++ G [y7] - 819.4611+[2] 977307 L [y5] - 633.3970+[3]
820582 Y [y4] - 520.3130+[4] 400762 L [y3] - 357.2496+[5] 498958 P
[y2] - 244.1656+[1] 1320591 I [b2] - 243.1339+[6] 303268 G [b3] -
300.1554+[7] 305120 alpha-1-antichymotrypsin R.GTHVDLGLASA
742.3794+++ D [y8] - 990.4931+[1] 154927 NVDFAFSLYK.Q L [b8] -
793.4203+[2] 51068 D [b5] - 510.2307+[3] 45310 F [y7] -
875.4662+[4] 42630 A [b9] - 864.4574+[5] 43355 S [y4] -
510.2922+[6] 45310 F [y5] - 657.3606+[7] 37330 V [y9] -
1089.5615+[8] 32491 G [b7] - 680.3362+[9] 38185 Y [y2] -
310.1761+[10] 36336 N [b12] - 16389 1136.5695+[11] S [b10] -
951.4894+[12] 16365 L [b6] - 623.3148+[13] 13687 L [y3] -
423.2602+[14] 17156 V [b4] - 395.2037+[15] 10964
alpha-1-antichymotrypsin R.NLAVSQVVHK.A 547.8195++ A [y8] -
867.5047+[1] 266203 L [b2] - 228.1343+[2] 314232 V [y7] -
796.4676+[3] 165231 A [b3] - 299.1714+[4] 173694 S [y6] -
697.3991+[5] 158512 H [y2] - 284.1717+[6] 136431 V [b4] -
398.2398+[7] 36099 S [b5] - 485.2718+[8] 23836 365.5487+++ S [y6] -
697.3991+[1] 223443 V [y3] - 383.2401+[2] 112952 V [y4] -
482.3085+[3] 84872 Q [y5] - 610.3671+[4] 30835 inter-alpha-trypsin
K.AAISGENAGLVR 579.3173++ S [y9] - 902.4690+[1] 518001 inhibitor
heavy chain H1 .A G [y8] - 815.4370+[2] 326256 N [y6] -
629.3729+[3] 296670 S [b4] - 343.1976+[4] 258172
inter-alpha-trypsin K.GSLVQASEANL 668.6763+++ A [y7] - 806.4155+[1]
304374 inhibitor heavy chain H1 QAAQDFVR.G A [y6] - 735.3784+[2]
193844 V [b4] - 357.2132+[3] 294094 F [y3] - 421.2558+[4] 167816 A
[b6] - 556.3089+[5] 149216 L [b11] - 535.7775++[6] 156882 A [b13] -
635.3253++[7] 249287 A [y14] - 760.3786++[8] 123723 F [b17] -
865.9208++[9] 23057 inter-alpha-trypsin K.TAFISDFAVTAD 1087.0442++
G [y4] - 432.2453+[1] 22362 inhibitor heavy chain H1 GNAFIGDIK.D I
[y5] - 545.3293+[2] 8319 A [b8] - 853.4090+[3] 7006 G [y9] -
934.4993+[4] 6755 F [y6] - 692.3978+[5] 6193 V [b9] - 952.4775+[6]
9508 inter-alpha-trypsin K.VTYDVSR.D 420.2165++ Y [y5] -
639.3097+[1] 609348 inhibitor heavy chain H1 T [b2] - 201.1234+[2]
792556 D [y4] - 476.2463+[3] 169546 V [y3] - 361.2194+[4] 256946 Y
[y5] - 320.1585++[5] 110608 S [y2] - 262.1510+[6] 50268 Y [b3] -
182.5970++[7] 10947 D [b4] - 479.2136+[8] 13662 inter-alpha-trypsin
R.EVAFDLEIPK.T 580.8135++ P [y2] - 244.1656+[1] 2032509 inhibitor
heavy chain H1 D [y6] - 714.4032+[2] 672749 A [y8] - 932.5088+[3]
390837 L [y5] - 599.3763+[4] 255527 F [y7] - 861.4716+[5] 305087
inter-alpha-trypsin R.LWAYLTIQELLA 781.4531++ W [b2] - 300.1707+[1]
602601 inhibitor heavy chain H1 K.R A [b3] - 371.2078+[2] 356967 T
[y8] - 915.5510+[3] 150419 Y [b4] - 534.2711+[4] 103449 I [y7] -
814.5033+[5] 72044 Q [y6] - 701.4192+[6] 66989 L [b5] -
647.3552+[7] 99820 E [y5] - 573.3606+[8] 44843 inter-alpha-trypsin
K.FYNQVSTPLLR.N 669.3642++ S [y6] - 686.4196+[1] 367330 inhibitor
heavy chain H2 V [y7] - 785.4880+[2] 182396 P [y4] - 498.3398+[3]
103638 Y [b2] - 311.1390+[4] 52172 Q [b4] - 553.2405+[5] 54270 N
[b3] - 425.1819+[6] 34567 inter-alpha-trypsin K.HLEVDVWVIEP
597.3247+++ I [y7] - 812.4625+[1] 206996 inhibitor heavy chain H2
QGLR.F P [y5] - 570.3358+[2] 303693 E [y6] - 699.3784+[3] 126752 P
[y5] - 285.6715++[4] 79841 inter-alpha-trypsin K.TAGLVR.S
308.6925++ A [b2] - 173.0921+[1] 460019 inhibitor heavy chain H2 G
[y4] - 444.2929+[2] 789068 V [y2] - 274.1874+[3] 34333 G [b3] -
230.1135+[4] 15169 L [y3] - 387.2714+[5] 29020 inter-alpha-trypsin
R.IYLQPGR.L 423.7452++ L [y5] - 570.3358+[1] 638209 inhibitor heavy
chain H2 P [y3] - 329.1932+[2] 235194 Y [b2] - 277.1547+[3] 266889
Q [y4] - 457.2518+[4] 171389 inter-alpha-trypsin R.LSNENHGIAQR.I
413.5461+++ N [y9] - 519.7574++[1] 325409 inhibitor heavy chain H2
N [y7] - 398.2146++[2] 39521 G [y5] - 544.3202+[3] 139598 S [b2] -
201.1234+[4] 54786 E [y8] - 462.7359++[5] 30623 inter-alpha-trypsin
R.SLAPTAAAKR.R 415.2425++ A [y7] - 629.3617+[1] 582421 inhibitor
heavy chain H2 L [b2] - 201.1234+[2] 430584 P [y6] - 558.3246+[3]
463815 A [b3] - 272.1605+[4] 204183 T [y5] - 461.2718+[5] 47301
inter-alpha-trypsin K.EVSFDVELPK.T 581.8032++ P [y2] - 244.1656+[1]
132304 inhibitor heavy chain H3 V [b2] - 229.1183+[2] 48895 L [y3]
- 357.2496+[3] 20685 inter-alpha-trypsin K.IQENVR.N 379.7114++ E
[y4] - 517.2729+[1] 190296 inhibitor heavy chain H3 E [b3] -
371.1925+[2] 51697 Q [b2] - 242.1499+[3] 54241 N [y3] -
388.2303+[4] 21156 V [y2] - 274.1874+[5] 8309 inter-alpha-trypsin
R.ALDLSLK.Y 380.2342++ D [y5] - 575.3399+[1] 687902 inhibitor heavy
chain H3 L [b2] - 185.1285+[2] 241010 L [y2] - 260.1969+[3] 29365
inter-alpha-trypsin R.LIQDAVTGLTVN 972.0258++ V [b6] - 640.3665+[1]
139259 inhibitor heavy chain H3 GQITGDK.R G [b8] - 798.4356+[2]
53886 G [y7] - 718.3730+[3] 12518 pigment epithelium- K.SSFVAPLEK.S
489.2687++ A [y5] - 557.3293+[1] 13436 derived factor precursor V
[y6] - 656.3978+[2] 9350 F [y7] - 803.4662+[3] 6672 P [y4] -
486.2922+[4] 6753 pigment epithelium- K.TVQAVLTVPK.L 528.3266++ Q
[y8] - 855.5298+[1] 26719 derived factor precursor V [b2] -
201.1234+[2] 21239 Q [y8] - 428.2686++[3] 16900 A [y7] -
727.4713+[4] 9518 L [y5] - 557.3657+[5] 5108 Q [b3] - 329.1819+[6]
5450 V [y6] - 656.4341+[7] 4391 pigment epithelium- R.ALYYDLISSPDIH
652.6632+++ Y [y15] - 886.4305++[1] 78073 derived factor precursor
GTYK.E Y [y14] - 804.8988++[2] 26148 pigment epithelium-
R.DTDTGALLFIGK.I 625.8350++ G [y8] - 818.5135+[1] 25553 derived
factor precursor T [b2] - 217.0819+[2] 22716 T [b4] - 217.0819++[3]
22716 L [y5] - 577.3708+[4] 11600 I [y3] - 317.2183+[5] 11089 A
[b6] - 561.2151+[6] 6956 pigment epithelium- K.ELLDTVTAPQK.N
607.8350++ T [y5] - 544.3089+[1] 17139 derived factor precursor D
[y8] - 859.4520+[2] 17440 L [y9] - 972.5360+[3] 14344 A [y4] -
443.2613+[4] 11474 T [y7] - 744.4250+[5] 10808 V [y6] -
643.3774+[6] 9064 pregnancy-specific beta- K.FQLPGQK.L 409.2320++ L
[y5] - 542.3297+[1] 116611 1-glycoprotein 1 P [y4] - 429.2456+[2]
91769 Q [b2] - 276.1343+[3] 93301 pregnancy-specific beta-
R.DLYHYITSYVVD 955.4762+++ G [y7] - 707.3471+[1] 5376
1-glycoprotein 1 GEIIIYGPAYSGR.E Y [y8] - 870.4104+[2] 3610 P [y6]
- 650.3257+[3] 2770 I [y9] - 983.4945+[4] 3361 pregnancy-specific
beta- K.LFIPQITPK.H 528.8262++ P [y6] - 683.4087+[1] 39754
1-glycoprotein 11 F [b2] - 261.1598+[2] 29966 I [y7] - 796.4927+[3]
13162 pregnancy-specific beta- NSATGEESSTSLTIR 776.8761++ E [b7] -
689.2737+[1] 11009 1-glycoprotein 11 T [y6] - 690.4145+[2] 11284 L
[y4] - 502.3348+[3] 2265 S [y7] - 389.2269++[4] 1200 T [y3] -
389.2507+[5] 1200 I [y2] - 288.2030+[6] 2248 pregnancy-specific
beta- K.FQQSGQNLFIP 617.3317+++ F [y8] - 474.2817++[1] 43682
1-glycoprotein 2 QITTK.H G [y12] - 680.3852++[2] 24166 S [b4] -
491.2249+[3] 23548 Q [b3] - 404.1928+[4] 17499 I [y4] -
462.2922+[5] 17304 F [b9] - 525.7538++[6] 17206 I [b10] -
582.2958++[7] 16718 L [b8] - 452.2196++[8] 16490
P [y6] - 344.2054++[9] 16198 G [b5] - 548.2463+[10] 15320
pregnancy-specific beta- IHPSYTNYR 575.7856++ N [b7] - 813.3890+[1]
16879 1-glycoprotein 2 Y [b5] - 598.2984+[2] 18087 T [y4] -
553.2729+[3] 2682 pregnancy-specific beta- FQLSETNR 497.7513++ L
[y6] - 719.3682+[1] 358059 1-glycoprotein 2 S [y5] - 606.2842+[2]
182330 Q [b2] - 276.1343+[3] 292482 pregnancy-specific beta-
VSAPSGTGHLPGL 506.2755+++ T [b7] - 300.6530++[1] 25346
1-glycoprotein 3 NPL H [y8] - 860.4989+[2] 12159 H [y8] -
430.7531++[3] 15522 pregnancy-specific beta- EDAGSYTLHIVK
666.8433++ Y [b6] - 623.2307+[1] 23965 1-glycoprotein 3 Y [y7] -
873.5193+[2] 21686 L [b8] - 837.3625+[3] 4104 A [b3] - 316.1139+[4]
1987 pregnancy-specific beta- R.TLFIFGVTK.Y 513.3051++ F [y7] -
811.4713+[1] 62145 1-glycoprotein 4 L [b2] - 215.1390+[2] 31687 F
[y5] - 551.3188+[3] 972 pregnancy-specific beta- NYTYIWWLNGQS
1097.5576++ W [b6] - 841.3879+[1] 25756 1-glycoprotein 4 LPVSPR G
[y9] - 940.5211+[2] 25018 Y [b4] - 542.2245+[3] 19778 Q [y8] -
883.4996+[4] 6642 P [y2] - 272.1717+[5] 5018 pregnancy-specific
beta- GVTGYFTFNLYLK 508.2695+++ L [y2] - 260.1969+[1] 176797
1-glycoprotein 5 T [y11] - 683.8557++[2] 136231 F [b6] -
625.2980+[3] 47523 L [y4] - 536.3443+[4] 23513 pregnancy-specific
beta- SNPVTLNVLYGPD 585.6527+++ Y [y7] - 817.4203+[1] 14118
1-glycoprotein 6 LPR G [y6] - 654.3570+[2] 10433 P [b3] -
299.1350+[3] 87138* P [y5] - 299.1714++[4] 77478* P [y5] -
597.3355+[5] 68089* pregnancy-specific beta- DVLLLVHNLPQNL
791.7741+++ L [y8] - 1017.5516+[3] 141169 1-glycoprotein 7 TGHIWYK
G [y6] - 803.4199+[5] 115905 W [y3] - 496.2554+[6] 108565 P [y11] -
678.8566++[7] 105493 V [b2] - 215.1026+[1] 239492 L [b3] -
328.1867+[2] 204413 N [b8] - 904.5251+[4] 121880 pregnancy-specific
beta- YGPAYSGR 435.7089++ A [y5] - 553.2729+[1] 25743*
1-glycoprotein 7 Y [y4] - 482.2358+[2] 25580* P [y6] - 650.3257+[3]
10831* S [y3] - 319.1724+[4] 10559* G [b2] - 221.0921+[5] 7837*
pregnancy-specific beta- LQLSETNR 480.7591++ S [b4] - 442.2660+[1]
18766 1-glycoprotein 8 L [b3] - 355.2340+[2] 12050 Q [b2] -
242.1499+[3] 1339 T [b6] - 672.3563+[4] 2489 pregnancy-specific
beta- K.LFIPQITR.N 494.3029++ P [y5] - 614.3620+[1] 53829
1-glycoprotein 9 I [y6] - 727.4461+[2] 13731 I [b3] - 374.2438+[3]
4178 Q [y4] - 517.3093+[4] 2984 pregnancy-specific beta-
K.LPIPYITINNLNP 819.4723++ P [b2] - 211.1441+[1] 18814*
1-glycoprotein 9 R.E P [b4] - 211.1441++[2] 18814* T [b7] -
798.4760+[3] 17287* T [y8] - 941.5163+[4] 10205* Y [b5] -
584.3443+[5] 10136* N [y6] - 727.3846+[6] 9511* pregnancy-specific
beta- R.SNPVILNVLYGP 589.6648+++ P [y5] - 597.3355+[1] 3994
1-glycoprotein 9 DLPR.I Y [y7] - 817.4203+[2] 3743 G [y6] -
654.3570+[3] 3045 pregnancy-specific beta- DVLLLVHNLPQNL
810.4387+++ P [y7] - 960.4614+[1] 120212 1-glycoprotein 9 PGYFWYK V
[b2] - 215.1026+[2] 65494 L [b3] - 328.1867+[3] 54798
pregnancy-specific beta- SENYTYIWWLNG 846.7603+++ W [y15] -
834.4488++[1] 14788 1-glycoprotein 9 QSLPVSPGVK P [y4] -
200.6314++[2] 19000 Y [y17] - 972.5225++[3] 4596 L [b10] -
678.8166++[4] 2660 Y [b6] - 758.2992+[5] 1705 P [y4] - 400.2554+[6]
1847 Pan-PSG ILILPSVTR 506.3317++ P [y5] - 559.3198+[1] 484395 L
[b2] - 227.1754+[2] 102774 L [b4] - 227.1754++[3] 102774 I [y7] -
785.4880+[4] 90153 I [b3] - 340.2595+[5] 45515 L [y6] -
672.4039+[6] 40368 thyroxine-binding K.AQWANPFDPS 630.8040++ A [b4]
- 457.2194+[1] 30802 globulin precursor K.T S [y2] - 234.1448+[2]
28255 D [y4] - 446.2245+[3] 24933 thyroxine-binding K.AVLHIGEK.G
289.5080+++ I [y4] - 446.2609+[1] 220841 globulin precursor H [y5]
- 292.1636++[2] 303815 H [y5] - 583.3198+[3] 133795 V [b2] -
171.1128+[4] 166139 L [y6] - 348.7056++[5] 823533 thyroxine-binding
K.FLNDVK.T 368.2054++ N [y4] - 475.2511+[1] 296859 globulin
precursor V [y2] - 246.1812+[2] 219597 L [b2] - 261.1598+[3] 87504
thyroxine-binding K.FSISATYDLGATL 800.4351++ Y [y9] - 993.5615+[1]
34111 globulin precursor LK.M G [y6] - 602.3872+[2] 17012 D [y8] -
830.4982+ 45104 S [b2] - 235.1077+[4] 15480 thyroxine-binding
K.GWVDLFVPK.F 530.7949++ W [b2] - 244.1081+[1] 1261810 globulin
precursor P [y2] - 244.1656+[2] 1261810 V [b7] - 817.4243+[3]
517675 V [y7] - 817.4818+[4] 517675 D [y6] - 718.4134+[5] 306994 F
[b6] - 718.3559+[6] 306994 V [y3] - 343.2340+[7] 112565 V [b3] -
343.1765+[8] 112565 thyroxine-binding K.NALALFVLPK.E 543.3395++ A
[y7] - 787.5076+[1] 198085 globulin precursor L [b3] - 299.1714+[2]
199857 P [y2] - 244.1656+[3] 129799 L [y8] - 900.5917+[4] 111572 L
[y6] - 716.4705+[5] 88773 F [y5] - 603.3865+[6] 54020 L [y3] -
357.2496+[7] 43353 thyroxine-binding R.SILFLGK.V 389.2471++ L [y5]
- 577.3708+[1] 1878736 globulin precursor I [b2] - 201.1234+[2]
946031 G [y2] - 204.1343+[3] 424248 L [y3] - 317.2183+[4] 291162 F
[y4] - 464.2867+[5] 391171 AFP R.DFNQFSSGEK.N 386.8402+++ N [b3] -
189.0764++[1] 42543 S [y4] - 210.6081++[2] 21340 G [y3] -
333.1769+[3] 53766 N [b3] - 377.1456+[4] 58644 F [b2] -
263.1026+[5] 5301 AFP K.GYQELLEK.C 490.2584++ E [y5] - 631.3661+[1]
110518 L [y4] - 502.3235+[2] 74844 E [y2] - 276.1554+[3] 42924 E
[b4] - 478.1932+[4] 20953 AFP K.GEEELQK.Y 416.7060++ E [b2] -
187.0713+[1] 37843 E [y4] - 517.2980+[2] 56988 AFP K.FIYEIAR.R
456.2529++ I [y3] - 359.2401+[1] 34880 I [b2] - 261.1598+[2] 7931
AFP R.HPFLYAPTILLW 590.3348+++ I [y7] - 421.7660++[1] 11471 AAR.Y L
[y6] - 365.2239++[2] 5001 A [b6] - 365.1896++[3] 5001 L [y6] -
729.4406+[4] 3218 F [b3] - 382.1874+[5] 6536 A [b6] - 729.3719+[6]
3218 AFP R.TFQAITVTK.L 504.7898++ T [b6] - 662.3508+[1] 11241 T
[y4] - 448.2766+[2] 7541 A [b4] - 448.2191+[3] 7541 AFP K.LTTLER.G
366.7162++ T [y4] - 518.2933+[1] 7836 L [b4] - 215.1390++[2] 4205 T
[b2] - 215.1390+[3] 4205 AFP R.HPQLAVSVILR.V L[y2] - 288.2030+[1]
3781 I [y3] - 401.2871+[2] 2924 L [b4] - 476.2616+[3] 2647 AFP
K.LGEYYLQNAFLV 631.6646+++ G [b2] - 171.1128+[1] 10790 AYTK.K Y
[y3] - 411.2238+[2] 2303 F [b10] - 600.2902++[3] 1780 Y [b4] -
463.2187+[4] 2214 F [y7] - 421.2445++[6] 3072 PGH1 R.ILPSVPK.D
377.2471++ P [y5] - 527.3188+[1] 5340492 S [y4] - 430.2660+[5]
419777 P [y2] - 244.1656+[2] 4198508 P [y5] - 264.1630++[3] 2771328
L [b2] - 227.1754+[4] 2331263 PGH1 K.AEHPTWGDEQL 639.3026+++ E [b9]
- 512.2120++[1] 64350 FQTTR.L P [b4] - 218.1030++[2] 38282 L [b11]
- 632.7833++[3] 129128 G [y10] - 597.7911++[4] 19406 G [b7] -
779.3471+[5] 51467 T [y3] - 189.1108++[6] 10590 D [y9] -
569.2804++[7] 12460 L [y6] - 765.4254+[8] 6704 D [b8] -
447.6907++[9] 4893 P [b4] - 435.1987+[10] 8858 Q [y7] -
893.4839+[11] 6101 T [b5] - 268.6268++[12] 5456 T [b5] -
536.2463+[13] 5549 PGH1 R.LILIGETIK.I 500.3261++ G [y5] -
547.3086+[1] 7649 T [y3] - 361.2445+[2] 6680 E [y4] - 490.2871+[3]
5234 L [y7] - 773.4767+[4] 3342 PGH1 R.LQPFNEYR.K 533.7694++ N [b5]
- 600.3140+[1] 25963 F [b4] - 486.2711+[2] 6915 E [y3] -
467.2249+[3] 15079 *QTRAP5500 data, all other peak areas are from
Agilent 6490
[0182] Next, the top 2-10 transitions per peptide and up to 7
peptides per protein were selected for collision energy (CE)
optimization on the Agilent 6490. Using Skyline or MassHunter Qual
software, the optimized CE value for each transition was determined
based on the peak area or signal to noise. The two transitions with
the largest peak areas per peptide and at least two peptides per
protein were chosen for the final MRM method. Substitutions of
transitions with lower peak areas were made when a transition with
a larger peak area had a high background level or had a low m/z
value that has more potential for interference.
[0183] Lastly, the retention times of selected peptides were mapped
using the same column and gradient as our established sMRM assay.
The newly discovered analytes were subsequently added to the sMRM
method and used in a further hypothesis-dependent discovery study
described in Example 5 below.
[0184] The above method was typical for most proteins. However, in
some cases, the differentially expressed peptide identified in the
shotgun method did not uniquely identify a protein, for example, in
protein families with high sequence identity. In these cases, a MRM
method was developed for each family member. Also, let it be noted
that, for any given protein, peptides in addition to those found to
be significant and fragment ions not observed on the Orbitrap may
have been included in MRM optimization and added to the final sMRM
method if those yielded the best signal intensities.
Example 5
Study IV to Identify and Confirm Preterm Birth Biomarkers
[0185] A further hypothesis-dependent discovery study was performed
with the scheduled MRM assay used in Examples 3 but now augmented
with newly discovered analytes from the Example 4. Less robust
transitions (from the original 1708 described in Example 1) were
removed to improve analytical performance and make room for the
newly discovered analytes. Samples included approximately 30 cases
and 60 matched controls from each of three gestational periods
(early, 17-22 weeks, middle, 23-25 weeks and late, 26-28 weeks).
Log transformed peak areas for each transition were corrected for
run order and batch effects by regression. The ability of each
analyte to separate cases and controls was determined by
calculating univariate AUC values from ROC curves. Ranked
univariate AUC values (0.6 or greater) are reported for individual
gestational age window sample sets (Tables 12, 13, 15) and a
combination of the middle and late window (Table 14). Multivariate
classifiers were built using different subsets of analytes
(described below) by Lasso and Random Forest methods. Lasso
significant transitions correspond to those with non-zero
coefficients and Random Forest analye ranking was determined by the
Gini importance values (mean decrease in model accuracy if that
variable is removed). We report all analytes with non-zero Lasso
coefficients (Tables 16-32) and the top 30 analytes from each
Random Forest analysis (Tables 33-49). Models were built
considering the top univariate 32 or 100 analytes, the single best
univariate analyte for the top 50 proteins or all analytes. Lastly
1000 rounds of bootstrap resampling were performed and the nonzero
Lasso coefficients or Random Forest Gini importance values were
summed for each analyte amongst panels with AUCs of 0.85 or
greater.
TABLE-US-00013 TABLE 12 Early Window Individual Stats Transition
Protein AUC ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN 0.834
ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 0.822 FLNWIK_410.7_560.3
HABP2_HUMAN 0.820 ITLPDFTGDLR_624.3_920.5 LBP_HUMAN 0.808
SFRPFVPR_335.9_635.3 LBP_HUMAN 0.800
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 0.800
FSVVYAK_407.2_579.4 FETUA_HUMAN 0.796 ITGFLKPGK_320.9_429.3
LBP_HUMAN 0.796 AHYDLR_387.7_288.2 FETUA_HUMAN 0.796
FSVVYAK_407.2_381.2 FETUA_HUMAN 0.795 SFRPFVPR_335.9_272.2
LBP_HUMAN 0.795 DVLLLVHNLPQNLPGYFWYK_810.4_967.5 PSG9_HUMAN 0.794
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 0.794 QALEEFQK_496.8_680.3
CO8B_HUMAN 0.792 DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN 0.792
AHYDLR_387.7_566.3 FETUA_HUMAN 0.791 VFQFLEK_455.8_811.4 CO5_HUMAN
0.786 ITGFLKPGK_320.9_301.2 LBP_HUMAN 0.783 VFQFLEK_455.8_276.2
CO5_HUMAN 0.782 SLLQPNK_400.2_599.4 CO8A_HUMAN 0.781
VQTAHFK_277.5_431.2 CO8A_HUMAN 0.780 SDLEVAHYK_531.3_617.3
CO8B_HUMAN 0.777 SLLQPNK_400.2_358.2 CO8A_HUMAN 0.776
TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 0.776
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.774 DISEVVTPR_508.3_787.4
CFAB_HUMAN 0.774 VSEADSSNADWVTK_754.9_533.3 CFAB_HUMAN 0.773
LSSPAVITDK_515.8_743.4 PLMN_HUMAN 0.773
VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN 0.772
DVLLLVHNLPQNLPGYFWYK_810.4_594.3 PSG9_HUMAN 0.771
ALVLELAK_428.8_672.4 INHBE_HUMAN 0.770 FLNWIK_410.7_561.3
HABP2_HUMAN 0.770 LSSPAVITDK_515.8_830.5 PLMN_HUMAN 0.769
LPNNVLQEK_527.8_844.5 AFAM_HUMAN 0.769 VSEADSSNADWVTK_754.9_347.2
CFAB_HUMAN 0.768 HTLNQIDEVK_598.8_951.5 FETUA_HUMAN 0.767
TTSDGGYSFK_531.7_860.4 INHA_HUMAN 0.761 YENYTSSFFIR_713.8_756.4
IL12B_HUMAN 0.760 HTLNQIDEVK_598.8_958.5 FETUA_HUMAN 0.760
DISEVVTPR_508.3_472.3 CFAB_HUMAN 0.760
LIQDAVTGLTVNGQITGDK_972.0_640.4 ITIH3_HUMAN 0.759
EAQLPVIENK_570.8_699.4 PLMN_HUMAN 0.759 SLPVSDSVLSGFEQR_810.9_836.4
CO8G_HUMAN 0.757 AVLHIGEK_289.5_348.7 THBG_HUMAN 0.755
GLQYAAQEGLLALQSELLR_1037.1_929.5 LBP_HUMAN 0.752
FLQEQGHR_338.8_497.3 CO8G_HUMAN 0.750 LPNNVLQEK_527.8_730.4
AFAM_HUMAN 0.750 AVLHIGEK_289.5_292.2 THBG_HUMAN 0.749
QLYGDTGVLGR_589.8_501.3 CO8G_HUMAN 0.748 WWGGQPLWITATK_772.4_929.5
ENPP2_HUMAN 0.747 NADYSYSVWK_616.8_769.4 CO5_HUMAN 0.746
GLQYAAQEGLLALQSELLR_1037.1_858.5 LBP_HUMAN 0.746
SLPVSDSVLSGFEQR_810.9_723.3 CO8G_HUMAN 0.745 IEEIAAK_387.2_531.3
CO5_HUMAN 0.743 TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 0.742
WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN 0.742 FQLSETNR_497.8_605.3
PSG2_HUMAN 0.741 NIQSVNVK_451.3_674.4 GROA_HUMAN 0.741
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.740
LQGTLPVEAR_542.3_571.3 CO5_HUMAN 0.740 SGFSFGFK_438.7_732.4
CO8B_HUMAN 0.740 HELTDEELQSLFTNFANVVDK_817.1_906.5 AFAM_HUMAN 0.740
VQTAHFK_277.5_502.3 CO8A_HUMAN 0.739 YENYTSSFFIR_713.8_293.1
IL12B_HUMAN 0.739 AFTECCVVASQLR_770.9_574.3 CO5_HUMAN 0.736
EAQLPVIENK_570.8_329.2 PLMN_HUMAN 0.734 QALEEFQK_496.8_551.3
CO8B_HUMAN 0.734 DAQYAPGYDK_564.3_813.4 CFAB_HUMAN 0.734
TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN 0.734
IAIDLFK_410.3_635.4 HEP2_HUMAN 0.733 TASDFITK_441.7_781.4
GELS_HUMAN 0.731 YEFLNGR_449.7_606.3 PLMN_HUMAN 0.731
TVQAVLTVPK_528.3_428.3 PEDF_HUMAN 0.731 LIENGYFHPVK_439.6_627.4
F13B_HUMAN 0.730 DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 0.730
TVQAVLTVPK_528.3_855.5 PEDF_HUMAN 0.730 ALQDQLVLVAAK_634.9_289.2
ANGT_HUMAN 0.727 TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.727
SDLEVAHYK_531.3_746.4 CO8B_HUMAN 0.726 FLPCENK_454.2_550.2
IL10_HUMAN 0.725 HPWIVHWDQLPQYQLNR_744.0_1047.0 KS6A3_HUMAN 0.725
AFTECCVVASQLR_770.9_673.4 CO5_HUMAN 0.725 YGLVTYATYPK_638.3_843.4
CFAB_HUMAN 0.724 TLEAQLTPR_514.8_685.4 HEP2_HUMAN 0.724
DAQYAPGYDK_564.3_315.1 CFAB_HUMAN 0.724 QGHNSVFLIK_381.6_260.2
HEMO_HUMAN 0.722 HELTDEELQSLFTNFANVVDK_817.1_854.4 AFAM_HUMAN 0.722
TLEAQLTPR_514.8_814.4 HEP2_HUMAN 0.721 IEEIAAK_387.2_660.4
CO5_HUMAN 0.721 HFQNLGK_422.2_527.2 AFAM_HUMAN 0.721
IAPQLSTEELVSLGEK_857.5_333.2 AFAM_HUMAN 0.721
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.720
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.719 IAIDLFK_410.3_706.4
HEP2_HUMAN 0.719 FLQEQGHR_338.8_369.2 CO8G_HUMAN 0.719
ALQDQLVLVAAK_634.9_956.6 ANGT_HUMAN 0.718
IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN 0.717 YEFLNGR_449.7_293.1
PLMN_HUMAN 0.717 TASDFITK_441.7_710.4 GELS_HUMAN 0.716
DADPDTFFAK_563.8_825.4 AFAM_HUMAN 0.716 TLLPVSKPEIR_418.3_514.3
CO5_HUMAN 0.716 NADYSYSVWK_616.8_333.2 CO5_HUMAN 0.715
YGLVTYATYPK_638.3_334.2 CFAB_HUMAN 0.715 VNHVTLSQPK_374.9_459.3
B2MG_HUMAN 0.715 HYGGLTGLNK_530.3_759.4 PGAM1_HUMAN 0.714
DFHINLFQVLPWLK_885.5_400.2 CFAB_HUMAN 0.714
NCSFSIIYPVVIK_770.4_555.4 CRHBP_HUMAN 0.714
HPWIVHWDQLPQYQLNR_744.0_918.5 KS6A3_HUMAN 0.712
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.711
ALDLSLK_380.2_185.1 ITIH3_HUMAN 0.711 ALDLSLK_380.2_575.3
ITIH3_HUMAN 0.710 LDFHFSSDR_375.2_611.3 INHBC_HUMAN 0.709
TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.707 EVFSKPISWEELLQ_852.9_260.2
FA40A_HUMAN 0.706 IAPQLSTEELVSLGEK_857.5_533.3 AFAM_HUMAN 0.704
LIENGYFHPVK_439.6_343.2 F13B_HUMAN 0.703 NFPSPVDAAFR_610.8_775.4
HEMO_HUMAN 0.703 QLYGDTGVLGR_589.8_345.2 CO8G_HUMAN 0.702
LYYGDDEK_501.7_563.2 CO8A_HUMAN 0.702 FQLSETNR_497.8_476.3
PSG2_HUMAN 0.701 TGVAVNKPAEFTVDAK_549.6_977.5 FLNA_HUMAN 0.700
IPGIFELGISSQSDR_809.9_679.3 CO8B_HUMAN 0.700 TLFIFGVTK_513.3_215.1
PSG4_HUMAN 0.699
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 0.699 QVFAVQR_424.2_473.3
ELNE_HUMAN 0.699 AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN
0.699 DFNQFSSGEK_386.8_189.1 FETA_HUMAN 0.699
SVSLPSLDPASAK_636.4_473.3 APOB_HUMAN 0.699 GNGLTWAEK_488.3_634.3
C163B_HUMAN 0.698 LYYGDDEK_501.7_726.3 CO8A_HUMAN 0.698
NFPSPVDAAFR_610.8_959.5 HEMO_HUMAN 0.698 FAFNLYR_465.8_565.3
HEP2_HUMAN 0.697 SGFSFGFK_438.7_585.3 CO8B_HUMAN 0.696
DFHINLFQVLPWLK_885.5_543.3 CFAB_HUMAN 0.696 LQGTLPVEAR_542.3_842.5
CO5_HUMAN 0.694 GAVHVVVAETDYQSFAVLYLER_822.8_863.5 CO8G_HUMAN 0.694
TSESTGSLPSPFLR_739.9_716.4 PSMG1_HUMAN 0.694
YISPDQLADLYK_713.4_277.2 ENOA_HUMAN 0.694 ESDTSYVSLK_564.8_347.2
CRP_HUMAN 0.693 ILDDLSPR_464.8_587.3 ITIH4_HUMAN 0.693
VQEAHLTEDQIFYFPK_655.7_391.2 CO8G_HUMAN 0.692
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 0.692 DTDTGALLFIGK_625.8_217.1
PEDF_HUMAN 0.692 HFQNLGK_422.2_285.1 AFAM_HUMAN 0.691
NNQLVAGYLQGPNVNLEEK_700.7_999.5 IL1RA_HUMAN 0.691
IPGIFELGISSQSDR_809.9_849.4 CO8B_HUMAN 0.691 ESDTSYVSLK_564.8_696.4
CRP_HUMAN 0.690 GAVHVVVAETDYQSFAVLYLER_822.8_580.3 CO8G_HUMAN 0.690
DADPDTFFAK_563.8_302.1 AFAM_HUMAN 0.690 LDFHFSSDR_375.2_464.2
INHBC_HUMAN 0.689 TLFIFGVTK_513.3_811.5 PSG4_HUMAN 0.688
DFNQFSSGEK_386.8_333.2 FETA_HUMAN 0.687 IQTHSTTYR_369.5_627.3
F13B_HUMAN 0.686 HYFIAAVER_553.3_658.4 FA8_HUMAN 0.686
VNHVTLSQPK_374.9_244.2 B2MG_HUMAN 0.686 DLHLSDVFLK_396.2_366.2
CO6_HUMAN 0.685 DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 0.684
AGITIPR_364.2_272.2 IL17_HUMAN 0.684 IAQYYYTFK_598.8_884.4
F13B_HUMAN 0.684 SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 0.683
VEPLYELVTATDFAYSSTVR_754.4_549.3 CO8B_HUMAN 0.682
AGITIPR_364.2_486.3 IL17_HUMAN 0.682 YEVQGEVFTKPQLWP_911.0_293.1
CRP_HUMAN 0.681 APLTKPLK_289.9_357.2 CRP_HUMAN 0.681
YNSQLLSFVR_613.8_508.3 TFR1_HUMAN 0.681
ANDQYLTAAALHNLDEAVK_686.4_301.1 IL1A_HUMAN 0.681
IQTHSTTYR_369.5_540.3 F13B_HUMAN 0.681 IHPSYTNYR_575.8_598.3
PSG2_HUMAN 0.681 TEFLSNYLTNVDDITLVPGTLGR_846.8_699.4 ENPP2_HUMAN
0.681 DPTFIPAPIQAK_433.2_461.2 ANGT_HUMAN 0.679
FQSVFTVTR_542.8_623.4 C1QC_HUMAN 0.679 LQVNTPLVGASLLR_741.0_925.6
BPIA1_HUMAN 0.679 DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 0.678
HATLSLSIPR_365.6_272.2 VGFR3_HUMAN 0.678 EDTPNSVWEPAK_686.8_315.2
C1S_HUMAN 0.678 TGISPLALIK_506.8_741.5 APOB_HUMAN 0.678
ILPSVPK_377.2_244.2 PGH1_HUMAN 0.676 HATLSLSIPR_365.6_472.3
VGFR3_HUMAN 0.676 QGHNSVFLIK_381.6_520.4 HEMO_HUMAN 0.676
LPATEKPVLLSK_432.6_460.3 HYOU1_HUMAN 0.675 APLTKPLK_289.9_398.8
CRP_HUMAN 0.674 GVTGYFTFNLYLK_508.3_683.9 PSG5_HUMAN 0.673
TFLTVYWTPER_706.9_401.2 ICAM1_HUMAN 0.673
GDTYPAELYITGSILR_885.0_274.1 F13B_HUMAN 0.672
EDTPNSVWEPAK_686.8_630.3 C1S_HUMAN 0.672 SLDFTELDVAAEK_719.4_316.2
ANGT_HUMAN 0.672 VELAPLPSWQPVGK_760.9_342.2 ICAM1_HUMAN 0.671
GPGEDFR_389.2_322.2 PTGDS_HUMAN 0.670 TDAPDLPEENQAR_728.3_843.4
CO5_HUMAN 0.670 GVTGYFTFNLYLK_508.3_260.2 PSG5_HUMAN 0.669
FAFNLYR_465.8_712.4 HEP2_HUMAN 0.669 ITENDIQIALDDAK_779.9_873.5
APOB_HUMAN 0.669 ILNIFGVIK_508.8_790.5 TFR1_HUMAN 0.669
ISQGEADINIAFYQR_575.6_684.4 MMP8_HUMAN 0.668
GDTYPAELYITGSILR_885.0_1332.8 F13B_HUMAN 0.668
ELLESYIDGR_597.8_710.4 THRB_HUMAN 0.668 FTITAGSK_412.7_576.3
FABPL_HUMAN 0.667 ILDGGNK_358.7_490.2 CXCL5_HUMAN 0.667
GWVTDGFSSLK_598.8_854.4 APOC3_HUMAN 0.667 FSLVSGWGQLLDR_493.3_403.2
FA7_HUMAN 0.665 IHPSYTNYR_575.8_813.4 PSG2_HUMAN 0.665
ELLESYIDGR_597.8_839.4 THRB_HUMAN 0.665 SDGAKPGPR_442.7_213.6
COLI_HUMAN 0.664 IAQYYYTFK_598.8_395.2 F13B_HUMAN 0.664
SILFLGK_389.2_201.1 THBG_HUMAN 0.664
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 0.664
VSAPSGTGHLPGLNPL_506.3_300.7 PSG3_HUMAN 0.664
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 0.664
YYGYTGAFR_549.3_771.4 TRFL_HUMAN 0.663 TDAPDLPEENQAR_728.3_613.3
CO5_HUMAN 0.663 IEVIITLK_464.8_815.5 CXL11_HUMAN 0.662
ILPSVPK_377.2_227.2 PGH1_HUMAN 0.662 FGFGGSTDSGPIR_649.3_745.4
ADA12_HUMAN 0.661 DYWSTVK_449.7_347.2 APOC3_HUMAN 0.661
IEGNLIFDPNNYLPK_874.0_845.5 APOB_HUMAN 0.661
WILTAAHTLYPK_471.9_407.2 C1R_HUMAN 0.661 WNFAYWAAHQPWSR_607.3_545.3
PRG2_HUMAN 0.661 SILFLGK_389.2_577.4 THBG_HUMAN 0.661
FSLVSGWGQLLDR_493.3_516.3 FA7_HUMAN 0.661 DTDTGALLFIGK_625.8_818.5
PEDF_HUMAN 0.661 SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.660
LWAYLTIQELLAK_781.5_371.2 ITIH1_HUMAN 0.660 LLEVPEGR_456.8_356.2
C1S_HUMAN 0.659 ITENDIQIALDDAK_779.9_632.3 APOB_HUMAN 0.659
LTTVDIVTLR_565.8_716.4 IL2RB_HUMAN 0.658 IEVIITLK_464.8_587.4
CXL11_HUMAN 0.658 QLGLPGPPDVPDHAAYHPF_676.7_299.2 ITIH4_HUMAN 0.658
TLAFVR_353.7_492.3 FA7_HUMAN 0.656 NSDQEIDFK_548.3_294.2
S10A5_HUMAN 0.656 YHFEALADTGISSEFYDNANDLLSK_940.8_874.5 CO8A_HUMAN
0.656 SEPRPGVLLR_375.2_454.3 FA7_HUMAN 0.655 FLPCENK_454.2_390.2
IL10_HUMAN 0.654 NCSFSIIYPVVIK_770.4_831.5 CRHBP_HUMAN 0.654
SLDFTELDVAAEK_719.4_874.5 ANGT_HUMAN 0.654
ILLLGTAVESAWGDEQSAFR_721.7_909.4 CXA1_HUMAN 0.653
SVSLPSLDPASAK_636.4_885.5 APOB_HUMAN 0.653 TGISPLALIK_506.8_654.5
APOB_HUMAN 0.653 YNQLLR_403.7_288.2 ENOA_HUMAN 0.653
YEVQGEVFTKPQLWP_911.0_392.2 CRP_HUMAN 0.652
VPGLYYFTYHASSR_554.3_720.3 C1QB_HUMAN 0.650
SLQNASAIESILK_687.4_589.4 IL3_HUMAN 0.650 WILTAAHTLYPK_471.9_621.4
C1R_HUMAN 0.650 GWVTDGFSSLK_598.8_953.5 APOC3_HUMAN 0.650
YGIEEHGK_311.5_599.3 CXA1_HUMAN 0.649 QDLGWK_373.7_503.3
TGFB3_HUMAN 0.649 DYWSTVK_449.7_620.3 APOC3_HUMAN 0.648
ALVLELAK_428.8_331.2 INHBE_HUMAN 0.647
QLGLPGPPDVPDHAAYHPF_676.7_263.1 ITIH4_HUMAN 0.646
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.645 TFLTVYWTPER_706.9_502.3
ICAM1_HUMAN 0.644 FQSVFTVTR_542.8_722.4 C1QC_HUMAN 0.643
DPNGLPPEAQK_583.3_669.4 RET4_HUMAN 0.642 ETLLQDFR_511.3_322.2
AMBP_HUMAN 0.642 IIEVEEEQEDPYLNDR_996.0_777.4 FBLN1_HUMAN 0.641
ELCLDPK_437.7_359.2 IL8_HUMAN 0.641 TPSAAYLWVGTGASEAEK_919.5_849.4
GELS_HUMAN 0.641 NQSPVLEPVGR_598.3_866.5 KS6A3_HUMAN 0.641
FNAVLTNPQGDYDTSTGK_964.5_333.2 C1QC_HUMAN 0.641
LLEVPEGR_456.8_686.4 C1S_HUMAN 0.641 FFQYDTWK_567.8_840.4
IGF2_HUMAN 0.640 SPEAEDPLGVER_649.8_670.4 Z512B_HUMAN 0.639
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.639 SGAQATWTELPWPHEK_613.3_793.4
HEMO_HUMAN 0.638 YSHYNER_323.5_581.3 HABP2_HUMAN 0.638
YHFEALADTGISSEFYDNANDLLSK_940.8_301.1 CO8A_HUMAN 0.637
DLHLSDVFLK_396.2_260.2 CO6_HUMAN 0.637 YSHYNER_323.5_418.2
HABP2_HUMAN 0.637 YYLQGAK_421.7_327.1 ITIH4_HUMAN 0.636
EVPLSALTNILSAQLISHWK_740.8_996.6 PAI1_HUMAN 0.636
VPGLYYFTYHASSR_554.3_420.2 C1QB_HUMAN 0.636
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 0.636
ETLLQDFR_511.3_565.3 AMBP_HUMAN 0.635
IVLSLDVPIGLLQILLEQAR_735.1_503.3 UCN2_HUMAN 0.635
ENPAVIDFELAPIVDLVR_670.7_811.5 CO6_HUMAN 0.635 LQLSETNR_480.8_355.2
PSG8_HUMAN 0.635 DPDQTDGLGLSYLSSHIANVER_796.4_456.2 GELS_HUMAN
0.635 NVNQSLLELHK_432.2_656.3 FRIH_HUMAN 0.634
EIGELYLPK_531.3_633.4 AACT_HUMAN 0.634 SPEQQETVLDGNLIIR_906.5_699.3
ITIH4_HUMAN 0.634 NKPGVYTDVAYYLAWIR_677.0_545.3 FA12_HUMAN 0.632
QNYHQDSEAAINR_515.9_544.3 FRIH_HUMAN 0.632
EKPAGGIPVLGSLVNTVLK_631.4_930.6 BPIB1_HUMAN 0.632
VTFEYR_407.7_614.3 CRHBP_HUMAN 0.630 DLPHITVDR_533.3_490.3
MMP7_HUMAN 0.630 VEHSDLSFSK_383.5_234.1 B2MG_HUMAN 0.630
ENPAVIDFELAPIVDLVR_670.7_601.4 CO6_HUMAN 0.630
YGFYTHVFR_397.2_659.4 THRB_HUMAN 0.629 ILDDLSPR_464.8_702.3
ITIH4_HUMAN 0.629 DPNGLPPEAQK_583.3_497.2 RET4_HUMAN 0.629
GSLVQASEANLQAAQDFVR_668.7_806.4 ITIH1_HUMAN 0.629 FLYHK_354.2_447.2
AMBP_HUMAN 0.627 FNAVLTNPQGDYDTSTGK_964.5_262.1 C1QC_HUMAN 0.627
LQDAGVYR_461.2_680.3 PD1L1_HUMAN 0.627 INPASLDK_429.2_630.4
C163A_HUMAN 0.626 LEEHYELR_363.5_580.3 PAI2_HUMAN 0.625
VEHSDLSFSK_383.5_468.2 B2MG_HUMAN 0.624 TSDQIHFFFAK_447.6_659.4
ANT3_HUMAN 0.624 ATLSAAPSNPR_542.8_570.3 CXCL2_HUMAN 0.624
YGFYTHVFR_397.2_421.3 THRB_HUMAN 0.624 EANQSTLENFLER_775.9_678.4
IL4_HUMAN 0.623 GQQPADVTGTALPR_705.9_314.2 CSF1_HUMAN 0.623
VELAPLPSWQPVGK_760.9_400.3 ICAM1_HUMAN 0.622
GEVTYTTSQVSK_650.3_750.4 EGLN_HUMAN 0.622 SLQAFVAVAAR_566.8_487.3
IL23A_HUMAN 0.622 HYGGLTGLNK_530.3_301.1 PGAM1_HUMAN 0.622
GPEDQDISISFAWDK_854.4_753.4 DEF4_HUMAN 0.622
YVVISQGLDKPR_458.9_400.3 LRP1_HUMAN 0.621 LWAYLTIQELLAK_781.5_300.2
ITIH1_HUMAN 0.621 SGAQATWTELPWPHEK_613.3_510.3 HEMO_HUMAN 0.621
GTAEWLSFDVTDTVR_848.9_952.5 TGFB3_HUMAN 0.621 FFQYDTWK_567.8_712.3
IGF2_HUMAN 0.621 AHQLAIDTYQEFEETYIPK_766.0_634.4 CSH_HUMAN 0.620
LPATEKPVLLSK_432.6_347.2 HYOU1_HUMAN 0.620 NIQSVNVK_451.3_546.3
GROA_HUMAN 0.620 TAVTANLDIR_537.3_288.2 CHL1_HUMAN 0.619
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.616 QINSYVK_426.2_496.3
CBG_HUMAN 0.616 GFQALGDAADIR_617.3_288.2 TIMP1_HUMAN 0.615
WNFAYWAAHQPWSR_607.3_673.3 PRG2_HUMAN 0.615 NEIWYR_440.7_357.2
FA12_HUMAN 0.615 VLEPTLK_400.3_587.3 VTDB_HUMAN 0.614
YYLQGAK_421.7_516.3 ITIH4_HUMAN 0.614 ALNSIIDVYHK_424.9_774.4
S10A8_HUMAN 0.614 ETPEGAEAKPWYEPIYLGGVFQLEK_951.1_877.5 TNFA_HUMAN
0.614 LNIGYIEDLK_589.3_837.4 PAI2_HUMAN 0.614
NVNQSLLELHK_432.2_543.3 FRIH_HUMAN 0.613
ILLLGTAVESAWGDEQSAFR_721.7_910.6 CXA1_HUMAN 0.613
AALAAFNAQNNGSNFQLEEISR_789.1_633.3 FETUA_HUMAN 0.613
VLEPTLK_400.3_458.3 VTDB_HUMAN 0.613 VGEYSLYIGR_578.8_708.4
SAMP_HUMAN 0.613 DIPHWLNPTR_416.9_373.2 PAPP1_HUMAN 0.612
NEIVFPAGILQAPFYTR_968.5_357.2 ECE1_HUMAN 0.612
AEHPTWGDEQLFQTTR_639.3_765.4 PGH1_HUMAN 0.612
VEPLYELVTATDFAYSSTVR_754.4_712.4 CO8B_HUMAN 0.611
DEIPHNDIALLK_459.9_260.2 HABP2_HUMAN 0.611 QINSYVK_426.2_610.3
CBG_HUMAN 0.610 SWNEPLYHLVTEVR_581.6_614.3 PRL_HUMAN 0.610
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.610 FGFGGSTDSGPIR_649.3_946.5
ADA12_HUMAN 0.610 ANDQYLTAAALHNLDEAVK_686.4_317.2 IL1A_HUMAN 0.610
VRPQQLVK_484.3_609.4 ITIH4_HUMAN 0.609 IPKPEASFSPR_410.2_506.3
ITIH4_HUMAN 0.609 SPEQQETVLDGNLIIR_906.5_685.4 ITIH4_HUMAN 0.609
DDLYVSDAFHK_655.3_704.3 ANT3_HUMAN 0.609 ELPEHTVK_476.8_347.2
VTDB_HUMAN 0.609 FLYHK_354.2_284.2 AMBP_HUMAN 0.608
QRPPDLDTSSNAVDLLFFTDESGDSR_961.5_262.2 C1R_HUMAN 0.608
DPDQTDGLGLSYLSSHIANVER_796.4_328.1 GELS_HUMAN 0.608
NEIWYR_440.7_637.4 FA12_HUMAN 0.607 LQLSETNR_480.8_672.4 PSG8_HUMAN
0.606 GQVPENEANVVITTLK_571.3_462.3 CADH1_HUMAN 0.606
FTGSQPFGQGVEHATANK_626.0_521.2 TSP1_HUMAN 0.605
LEPLYSASGPGLRPLVIK_637.4_260.2 CAA60698 0.605
QRPPDLDTSSNAVDLLFFTDESGDSR_961.5_866.3 C1R_HUMAN 0.604
LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.604 TSDQIHFFFAK_447.6_512.3
ANT3_HUMAN 0.604 IQHPFTVEEFVLPK_562.0_861.5 PZP_HUMAN 0.603
NKPGVYTDVAYYLAWIR_677.0_821.5 FA12_HUMAN 0.603 TEQAAVAR_423.2_615.4
FA12_HUMAN 0.603 EIGELYLPK_531.3_819.5 AACT_HUMAN 0.602
LFYADHPFIFLVR_546.6_647.4 SERPH_HUMAN 0.602
AEHPTWGDEQLFQTTR_639.3_569.3 PGH1_HUMAN 0.601 TSYQVYSK_488.2_787.4
C163A_HUMAN 0.601 YTTEIIK_434.2_704.4 C1R_HUMAN 0.601
NVIQISNDLENLR_509.9_402.3 LEP_HUMAN 0.600
AFLEVNEEGSEAAASTAVVIAGR_764.4_685.4 ANT3_HUMAN 0.600
TABLE-US-00014 TABLE 13 Middle Window Individual Stats Transition
Protein AUC SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.738
VFQFLEK_455.8_811.4 CO5_HUMAN 0.709 ALNHLPLEYNSALYSR_621.0_696.4
CO6_HUMAN 0.705 SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 0.692
VEHSDLSFSK_383.5_234.1 B2MG_HUMAN 0.686
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 0.683
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.683 VLEPTLK_400.3_458.3
VTDB_HUMAN 0.681 LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 0.681
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.679 YGIEEHGK_311.5_599.3
CXA1_HUMAN 0.677 ALQDQLVLVAAK_634.9_289.2 ANGT_HUMAN 0.675
VLEPTLK_400.3_587.3 VTDB_HUMAN 0.667 VNHVTLSQPK_374.9_244.2
B2MG_HUMAN 0.665 IEEIAAK_387.2_660.4 CO5_HUMAN 0.664
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.664
TLLPVSKPEIR_418.3_514.3 CO5_HUMAN 0.662 ALQDQLVLVAAK_634.9_956.6
ANGT_HUMAN 0.661 TLAFVR_353.7_492.3 FA7_HUMAN 0.661
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.658 VEHSDLSFSK_383.5_468.2
B2MG_HUMAN 0.653 DPTFIPAPIQAK_433.2_461.2 ANGT_HUMAN 0.653
QGHNSVFLIK_381.6_260.2 HEMO_HUMAN 0.650 SLDFTELDVAAEK_719.4_874.5
ANGT_HUMAN 0.650 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN 0.649
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.647 SLQAFVAVAAR_566.8_804.5
IL23A_HUMAN 0.646 AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN
0.644 QGHNSVFLIK_381.6_520.4 HEMO_HUMAN 0.644
VNHVTLSQPK_374.9_459.3 B2MG_HUMAN 0.643 DLHLSDVFLK_396.2_260.2
CO6_HUMAN 0.643 TEQAAVAR_423.2_615.4 FA12_HUMAN 0.643
GPITSAAELNDPQSILLR_632.4_826.5 EGLN_HUMAN 0.643 HFQNLGK_422.2_527.2
AFAM_HUMAN 0.642 TEQAAVAR_423.2_487.3 FA12_HUMAN 0.642
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 0.642 TLFIFGVTK_513.3_811.5
PSG4_HUMAN 0.642 DLHLSDVFLK_396.2_366.2 CO6_HUMAN 0.641
AFTECCVVASQLR_770.9_574.3 CO5_HUMAN 0.640
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.639
DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 0.639 FSLVSGWGQLLDR_493.3_403.2
FA7_HUMAN 0.638 HYINLITR_515.3_301.1 NPY_HUMAN 0.637
HFQNLGK_422.2_285.1 AFAM_HUMAN 0.637 VPLALFALNR_557.3_620.4
PEPD_HUMAN 0.636 IHPSYTNYR_575.8_813.4 PSG2_HUMAN 0.635
IEEIAAK_387.2_531.3 CO5_HUMAN 0.635 GEVTYTTSQVSK_650.3_750.4
EGLN_HUMAN 0.634 DFNQFSSGEK_386.8_333.2 FETA_HUMAN 0.634
VVGGLVALR_442.3_784.5 FA12_HUMAN 0.634 SDGAKPGPR_442.7_459.2
COLI_HUMAN 0.634 DVLLLVHNLPQNLTGHIWYK_791.8_310.2 PSG7_HUMAN 0.634
TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 0.633
NKPGVYTDVAYYLAWIR_677.0_821.5 FA12_HUMAN 0.630 QVFAVQR_424.2_473.3
ELNE_HUMAN 0.630 NHYTESISVAK_624.8_415.2 NEUR1_HUMAN 0.630
IAPQLSTEELVSLGEK_857.5_333.2 AFAM_HUMAN 0.629 IHPSYTNYR_575.8_598.3
PSG2_HUMAN 0.627 EVFSKPISWEELLQ_852.9_260.2 FA40A_HUMAN 0.627
SILFLGK_389.2_201.1 THBG_HUMAN 0.626 IEVIITLK_464.8_587.4
CXL11_HUMAN 0.625 VVGGLVALR_442.3_685.4 FA12_HUMAN 0.624
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_598.4 SHBG_HUMAN 0.624
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 0.623
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_768.5 SHBG_HUMAN 0.622
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.621
LHEAFSPVSYQHDLALLR_699.4_380.2 FA12_HUMAN 0.621 AHYDLR_387.7_566.3
FETUA_HUMAN 0.620 FSVVYAK_407.2_381.2 FETUA_HUMAN 0.618
ALALPPLGLAPLLNLWAKPQGR_770.5_256.2 SHBG_HUMAN 0.618
YENYTSSFFIR_713.8_293.1 IL12B_HUMAN 0.617
VELAPLPSWQPVGK_760.9_342.2 ICAM1_HUMAN 0.617 SILFLGK_389.2_577.4
THBG_HUMAN 0.616 ILPSVPK_377.2_227.2 PGH1_HUMAN 0.615
IPSNPSHR_303.2_496.3 FBLN3_HUMAN 0.615 HYFIAAVER_553.3_301.1
FA8_HUMAN 0.615 FSVVYAK_407.2_579.4 FETUA_HUMAN 0.613
VFQFLEK_455.8_276.2 CO5_HUMAN 0.613 IAPQLSTEELVSLGEK_857.5_533.3
AFAM_HUMAN 0.613 ILPSVPK_377.2_244.2 PGH1_HUMAN 0.613
NKPGVYTDVAYYLAWIR_677.0_545.3 FA12_HUMAN 0.613
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.612
TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN 0.612
ALALPPLGLAPLLNLWAKPQGR_770.5_457.3 SHBG_HUMAN 0.612
QLGLPGPPDVPDHAAYHPF_676.7_299.2 ITIH4_HUMAN 0.612
ILDDLSPR_464.8_587.3 ITIH4_HUMAN 0.611 VELAPLPSWQPVGK_760.9_400.3
ICAM1_HUMAN 0.611 DADPDTFFAK_563.8_825.4 AFAM_HUMAN 0.611
NHYTESISVAK_624.8_252.1 NEUR1_HUMAN 0.611 SEPRPGVLLR_375.2_454.3
FA7_HUMAN 0.611 LNIGYIEDLK_589.3_950.5 PAI2_HUMAN 0.611
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.609 LTTVDIVTLR_565.8_716.4
IL2RB_HUMAN 0.608 TQILEWAAER_608.8_761.4 EGLN_HUMAN 0.608
NEPEETPSIEK_636.8_573.3 SOX5_HUMAN 0.608
AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN 0.607
LQVNTPLVGASLLR_741.0_925.6 BPIA1_HUMAN 0.607 VPSHAVVAR_312.5_345.2
TRFL_HUMAN 0.607 SLQNASAIESILK_687.4_860.5 IL3_HUMAN 0.607
GVTGYFTFNLYLK_508.3_260.2 PSG5_HUMAN 0.605 DFNQFSSGEK_386.8_189.1
FETA_HUMAN 0.605 QLGLPGPPDVPDHAAYHPF_676.7_263.1 ITIH4_HUMAN 0.605
TLEAQLTPR_514.8_814.4 HEP2_HUMAN 0.604 AFTECCVVASQLR_770.9_673.4
CO5_HUMAN 0.604 LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.604
TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.603 LWAYLTIQELLAK_781.5_300.2
ITIH1_HUMAN 0.603 GGLFADIASHPWQAAIFAK_667.4_375.2 TPA_HUMAN 0.603
IPSNPSHR_303.2_610.3 FBLN3_HUMAN 0.603 TDAPDLPEENQAR_728.3_843.4
CO5_HUMAN 0.603 SPQAFYR_434.7_684.4 REL3_HUMAN 0.602
SSNNPHSPIVEEFQVPYNK_729.4_261.2 C1S_HUMAN 0.601 AHYDLR_387.7_288.2
FETUA_HUMAN 0.600 DGSPDVTTADIGANTPDATK_973.5_844.4 PGRP2_HUMAN
0.600 SPQAFYR_434.7_556.3 REL3_HUMAN 0.600
TABLE-US-00015 TABLE 14 Middle Late Individual Stats Transition
Protein AUC ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.656
VPLALFALNR_557.3_620.4 PEPD_HUMAN 0.655
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.652 AVYEAVLR_460.8_587.4
PEPD_HUMAN 0.649 SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.644
VFQFLEK_455.8_811.4 CO5_HUMAN 0.643
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.640
TLAFVR_353.7_492.3 FA7_HUMAN 0.639 TEQAAVAR_423.2_615.4 FA12_HUMAN
0.637 YGIEEHGK_311.5_599.3 CXA1_HUMAN 0.637 TEQAAVAR_423.2_487.3
FA12_HUMAN 0.633 QINSYVK_426.2_496.3 CBG_HUMAN 0.633
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.633 SEYGAALAWEK_612.8_845.5
CO6_HUMAN 0.633 ALQDQLVLVAAK_634.9_956.6 ANGT_HUMAN 0.628
VLEPTLK_400.3_587.3 VTDB_HUMAN 0.628 DFNQFSSGEK_386.8_333.2
FETA_HUMAN 0.628 TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.628
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 0.626 QINSYVK_426.2_610.3
CBG_HUMAN 0.625 SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 0.625
DPTFIPAPIQAK_433.2_461.2 ANGT_HUMAN 0.625 AVYEAVLR_460.8_750.4
PEPD_HUMAN 0.623 YENYTSSFFIR_713.8_756.4 IL12B_HUMAN 0.623
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.623
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.622
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.622
ALQDQLVLVAAK_634.9_289.2 ANGT_HUMAN 0.621 SLQAFVAVAAR_566.8_804.5
IL23A_HUMAN 0.621 DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 0.620
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 0.619 VLEPTLK_400.3_458.3
VTDB_HUMAN 0.619 SLDFTELDVAAEK_719.4_874.5 ANGT_HUMAN 0.618
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.618
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.618
TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN 0.615
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 0.615
TLEAQLTPR_514.8_685.4 HEP2_HUMAN 0.613 ELPQSIVYK_538.8_417.7
FBLN3_HUMAN 0.612 GYQELLEK_490.3_631.4 FETA_HUMAN 0.612
VPLALFALNR_557.3_917.6 PEPD_HUMAN 0.611 DLHLSDVFLK_396.2_260.2
CO6_HUMAN 0.611 LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.608
WSAGLTSSQVDLYIPK_883.0_357.2 CBG_HUMAN 0.608 ITQDAQLK_458.8_702.4
CBG_HUMAN 0.608 NIQSVNVK_451.3_674.4 GROA_HUMAN 0.607
ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN 0.607 TLNAYDHR_330.5_312.2
PAR3_HUMAN 0.606 LWAYLTIQELLAK_781.5_300.2 ITIH1_HUMAN 0.606
VVGGLVALR_442.3_784.5 FA12_HUMAN 0.605
AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN 0.603
SVVLIPLGAVDDGEHSQNEK_703.0_798.4 CNDP1_HUMAN 0.603
SETEIHQGFQHLHQLFAK_717.4_318.1 CBG_HUMAN 0.603
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 0.603
IEVIITLK_464.8_587.4 CXL11_HUMAN 0.602 ITQDAQLK_458.8_803.4
CBG_HUMAN 0.602 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 0.601
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 0.601 LTTVDIVTLR_565.8_716.4
IL2RB_HUMAN 0.600 WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 0.600
TABLE-US-00016 TABLE 15 Late Window Individual Stats Transition
Protein AUC AVYEAVLR_460.8_587.4 PEPD_HUMAN 0.724
AEIEYLEK_497.8_552.3 LYAM1_HUMAN 0.703 QINSYVK_426.2_496.3
CBG_HUMAN 0.695 AVYEAVLR_460.8_750.4 PEPD_HUMAN 0.693
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 0.684
QINSYVK_426.2_610.3 CBG_HUMAN 0.681 VPLALFALNR_557.3_620.4
PEPD_HUMAN 0.678 VGVISFAQK_474.8_580.3 TFR2_HUMAN 0.674
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.670
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.670 LIEIANHVDK_384.6_498.3
ADA12_HUMAN 0.660 SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 0.660
TSYQVYSK_488.2_787.4 C163A_HUMAN 0.657 ITQDAQLK_458.8_702.4
CBG_HUMAN 0.652 YYGYTGAFR_549.3_450.3 TRFL_HUMAN 0.650
ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN 0.650
VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN 0.650
SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 0.648 YENYTSSFFIR_713.8_756.4
IL12B_HUMAN 0.647 VLSSIEQK_452.3_691.4 1433S_HUMAN 0.647
YSHYNER_323.5_418.2 HABP2_HUMAN 0.646 ILDGGNK_358.7_603.3
CXCL5_HUMAN 0.645 GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.645
AEIEYLEK_497.8_389.2 LYAM1_HUMAN 0.645 TLPFSR_360.7_506.3
LYAM1_HUMAN 0.645 DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 0.644
ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN 0.644 SPEAEDPLGVER_649.8_314.1
Z512B_HUMAN 0.644 FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.642
TASDFITK_441.7_781.4 GELS_HUMAN 0.641
SETEIHQGFQHLHQLFAK_717.4_447.2 CBG_HUMAN 0.640 SPQAFYR_434.7_556.3
REL3_HUMAN 0.639 TAVTANLDIR_537.3_288.2 CHL1_HUMAN 0.636
VPLALFALNR_557.3_917.6 PEPD_HUMAN 0.636 YISPDQLADLYK_713.4_277.2
ENOA_HUMAN 0.633 SETEIHQGFQHLHQLFAK_717.4_318.1 CBG_HUMAN 0.633
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.633 GYQELLEK_490.3_631.4
FETA_HUMAN 0.633 AYSDLSR_406.2_375.2 SAMP_HUMAN 0.633
SVVLIPLGAVDDGEHSQNEK_703.0_798.4 CNDP1_HUMAN 0.632
TLEAQLTPR_514.8_685.4 HEP2_HUMAN 0.631 WSAGLTSSQVDLYIPK_883.0_515.3
CBG_HUMAN 0.631 TEQAAVAR_423.2_615.4 FA12_HUMAN 0.628
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.626
AGITIPR_364.2_486.3 IL17_HUMAN 0.626 AEVIWTSSDHQVLSGK_586.3_300.2
PD1L1_HUMAN 0.625 TEQAAVAR_423.2_487.3 FA12_HUMAN 0.625
NHYTESISVAK_624.8_415.2 NEUR1_HUMAN 0.625
WSAGLTSSQVDLYIPK_883.0_357.2 CBG_HUMAN 0.623 YSHYNER_323.5_581.3
HABP2_HUMAN 0.623 DFNQFSSGEK_386.8_333.2 FETA_HUMAN 0.621
NIQSVNVK_451.3_674.4 GROA_HUMAN 0.620
SVVLIPLGAVDDGEHSQNEK_703.0_286.2 CNDP1_HUMAN 0.620
TLAFVR_353.7_492.3 FA7_HUMAN 0.619 AVDIPGLEAATPYR_736.9_286.1
TENA_HUMAN 0.619 TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN
0.618 YWGVASFLQK_599.8_849.5 RET4_HUMAN 0.618
TPSAAYLWVGTGASEAEK_919.5_428.2 GELS_HUMAN 0.618
DPNGLPPEAQK_583.3_669.4 RET4_HUMAN 0.617 TYLHTYESEI_628.3_908.4
ENPP2_HUMAN 0.616 SPQAFYR_434.7_684.4 REL3_HUMAN 0.616
TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN 0.615
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.615
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 0.615
LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.615 LWAYLTIQELLAK_781.5_371.2
ITIH1_HUMAN 0.613 SYTITGLQPGTDYK_772.4_352.2 FINC_HUMAN 0.612
GAVHVVVAETDYQSFAVLYLER_822.8_863.5 CO8G_HUMAN 0.612
FQLPGQK_409.2_276.1 PSG1_HUMAN 0.612 ILDGGNK_358.7_490.2
CXCL5_HUMAN 0.611 DYWSTVK_449.7_620.3 APOC3_HUMAN 0.611
AGLLRPDYALLGHR_518.0_595.4 PGRP2_HUMAN 0.611
ALNFGGIGVVVGHELTHAFDDQGR_837.1_360.2 ECE1_HUMAN 0.611
GYQELLEK_490.3_502.3 FETA_HUMAN 0.611 HATLSLSIPR_365.6_472.3
VGFR3_HUMAN 0.610 SVPVTKPVPVTKPITVTK_631.1_658.4 Z512B_HUMAN 0.610
FQLPGQK_409.2_429.2 PSG1_HUMAN 0.610 IYLQPGR_423.7_329.2
ITIH2_HUMAN 0.610 TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.609
DPNGLPPEAQK_583.3_497.2 RET4_HUMAN 0.609 FGFGGSTDSGPIR_649.3_946.5
ADA12_HUMAN 0.609 TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.608
GAVHVVVAETDYQSFAVLYLER_822.8_580.3 CO8G_HUMAN 0.608
VPSHAVVAR_312.5_515.3 TRFL_HUMAN 0.608 YWGVASFLQK_599.8_350.2
RET4_HUMAN 0.608 EWVAIESDSVQPVPR_856.4_468.3 CNDP1_HUMAN 0.607
LQDAGVYR_461.2_680.3 PD1L1_HUMAN 0.607
DLYHYITSYVVDGEIIIYGPAYSGR_955.5_650.3 PSG1_HUMAN 0.607
LWAYLTIQELLAK_781.5_300.2 ITIH1_HUMAN 0.606
ITENDIQIALDDAK_779.9_632.3 APOB_HUMAN 0.606
SYTITGLQPGTDYK_772.4_680.3 FINC_HUMAN 0.606 FFQYDTWK_567.8_712.3
IGF2_HUMAN 0.605 IYLQPGR_423.7_570.3 ITIH2_HUMAN 0.605
YNQLLR_403.7_529.4 ENOA_HUMAN 0.605 WWGGQPLWITATK_772.4_929.5
ENPP2_HUMAN 0.605 WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN 0.605
TASDFITK_441.7_710.4 GELS_HUMAN 0.605 EWVAIESDSVQPVPR_856.4_486.2
CNDP1_HUMAN 0.605 YEFLNGR_449.7_606.3 PLMN_HUMAN 0.604
SNPVTLNVLYGPDLPR_585.7_654.4 PSG6_HUMAN 0.604 ITQDAQLK_458.8_803.4
CBG_HUMAN 0.603 LTTVDIVTLR_565.8_716.4 IL2RB_HUMAN 0.602
FNAVLTNPQGDYDTSTGK_964.5_262.1 C1QC_HUMAN 0.602
ITGFLKPGK_320.9_301.2 LBP_HUMAN 0.601 DYWSTVK_449.7_347.2
APOC3_HUMAN 0.601 DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 0.601
GWVTDGFSSLK_598.8_953.5 APOC3_HUMAN 0.601 YYGYTGAFR_549.3_771.4
TRFL_HUMAN 0.601 ELPEHTVK_476.8_347.2 VTDB_HUMAN 0.601
FTFTLHLETPKPSISSSNLNPR_829.4_874.4 PSG1_HUMAN 0.601
DLYHYITSYVVDGEIIIYGPAYSGR_955.5_707.3 PSG1_HUMAN 0.601
SPQAFYR_434.7_684.4 REL3_HUMAN 0.616 TPSAAYLWVGTGASEAEK_919.5_849.4
GELS_HUMAN 0.615 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.615
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 0.615
LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.615 LWAYLTIQELLAK_781.5_371.2
ITIH1_HUMAN 0.613 SYTITGLQPGTDYK_772.4_352.2 FINC_HUMAN 0.612
GAVHVVVAETDYQSFAVLYLER_822.8_863.5 CO8G_HUMAN 0.612
FQLPGQK_409.2_276.1 PSG1_HUMAN 0.612
DLYHYITSYVVDGEIIIYGPAYSGR_955.5_707.3 PSG1_HUMAN 0.601
TABLE-US-00017 TABLE 16 Lasso Early 32 Variable Protein Coefficient
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 9.53
VQTAHFK_277.5_431.2 CO8A_HUMAN 9.09 FLNWIK_410.7_560.3 HABP2_HUMAN
6.15 ITGFLKPGK_320.9_429.3 LBP_HUMAN 5.29
ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN 3.83
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 3.41 DISEVVTPR_508.3_787.4
CFAB_HUMAN 0.44 AHYDLR_387.7_288.2 FETUA_HUMAN 0.1
TABLE-US-00018 TABLE 17 Lasso Early 100 Variable Protein
Coefficient LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 6.56
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 6.51 VQTAHFK_277.5_431.2
CO8A_HUMAN 4.51 NIQSVNVK_451.3_674.4 GROA_HUMAN 3.12
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 2.68 LIENGYFHPVK_439.6_627.4
F13B_HUMAN 2.56 AVLHIGEK_289.5_292.2 THBG_HUMAN 2.11
FLNWIK_410.7_560.3 HABP2_HUMAN 1.85 ITGFLKPGK_320.9_429.3 LBP_HUMAN
1.36 DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 1.3
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.83 FLPCENK_454.2_550.2
IL10_HUMAN 0.39 ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN 0.3
TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN 0.29
VSEADSSNADWVTK_754.9_347.2 CFAB_HUMAN 0.27 ITLPDFTGDLR_624.3_288.2
LBP_HUMAN 0.13 TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.04
TASDFITK_441.7_781.4 GELS_HUMAN -5.91
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 6.56
TABLE-US-00019 TABLE 18 Lasso Protein Early Window Variable Protein
Coefficient ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 7.17
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 6.06
LIENGYFHPVK_439.6_627.4 F13B_HUMAN 3.23 WWGGQPLWITATK_772.4_929.5
ENPP2_HUMAN 2.8 QALEEFQK_496.8_680.3 CO8B_HUMAN 2.73
NIQSVNVK_451.3_674.4 GROA_HUMAN 2.53 DALSSVQESQVAQQAR_573.0_672.4
APOC3_HUMAN 2.51 AVLHIGEK_289.5_348.7 THBG_HUMAN 2.33
FLNWIK_410.7_560.3 HABP2_HUMAN 1.05 FLPCENK_454.2_550.2 IL10_HUMAN
0.74 ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 0.7 DISEVVTPR_508.3_787.4
CFAB_HUMAN 0.45 EVFSKPISWEELLQ_852.9_260.2 FA40A_HUMAN 0.17
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 0.06 TASDFITK_441.7_781.4
GELS_HUMAN -7.65
TABLE-US-00020 TABLE 19 Lasso All Early Window Variable Protein
Coefficient FLNWIK_410.7_560.3 HABP2_HUMAN 3.74 AHYDLR_387.7_288.2
FETUA_HUMAN 0.07 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 6.07
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 8.85
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 2.97 VQTAHFK_277.5_431.2
CO8A_HUMAN 3.36 ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 11.24
VSEADSSNADWVTK_754.9_347.2 CFAB_HUMAN 0.63 AVLHIGEK_289.5_292.2
THBG_HUMAN 0.51 TGVAVNKPAEFTVDAK_549.6_977.5 FLNA_HUMAN 0.17
LIENGYFHPVK_439.6_343.2 F13B_HUMAN 1.7
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN -0.93
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 1.4 TASDFITK_441.7_781.4
GELS_HUMAN -0.07 NIQSVNVK_451.3_674.4 GROA_HUMAN 2.12
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 1.15
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.09
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 2.45 ALDLSLK_380.2_575.3
ITIH3_HUMAN 2.51 TLFIFGVTK_513.3_811.5 PSG4_HUMAN 4.12
ISQGEADINIAFYQR_575.6_684.4 MMP8_HUMAN 1.29 SGVDLADSNQK_567.3_591.3
VGFR3_HUMAN 0.55 GPGEDFR_389.2_322.2 PTGDS_HUMAN 0.07
DPNGLPPEAQK_583.3_669.4 RET4_HUMAN 1.36 WNFAYWAAHQPWSR_607.3_545.3
PRG2_HUMAN -1.27 ELCLDPK_437.7_359.2 IL8_HUMAN 0.3
FFQYDTWK_567.8_840.4 IGF2_HUMAN 1.83 IIEVEEEQEDPYLNDR_996.0_777.4
FBLN1_HUMAN 1.14 ECEELEEK_533.2_405.2 IL15_HUMAN 1.78
LEEHYELR_363.5_580.3 PAI2_HUMAN 0.15 LNIGYIEDLK_589.3_837.4
PAI2_HUMAN 0.32 TAVTANLDIR_537.3_288.2 CHL1_HUMAN -0.98
SWNEPLYHLVTEVR_581.6_716.4 PRL_HUMAN 1.88 ILNIFGVIK_508.8_790.5
TFR1_HUMAN 0.05 TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN -2.69
VGVISFAQK_474.8_693.4 TFR2_HUMAN -5.68 LNIGYIEDLK_589.3_950.5
PAI2_HUMAN -1.43 GQVPENEANVVITTLK_571.3_462.3 CADH1_HUMAN -0.55
STPSLTTK_417.7_549.3 IL6RA_HUMAN -0.59 ALLLGWVPTR_563.3_373.2
PAR4_HUMAN -0.97
TABLE-US-00021 TABLE 20 Lasso SummedCoef Early Window Transition
Protein SumBestCoefs LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN
1173.723955 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 811.0150364
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 621.9659363
VQTAHFK_277.5_431.2 CO8A_HUMAN 454.178544 NIQSVNVK_451.3_674.4
GROA_HUMAN 355.9550674 TLFIFGVTK_513.3_811.5 PSG4_HUMAN 331.8629189
GPGEDFR_389.2_322.2 PTGDS_HUMAN 305.9079494 FLPCENK_454.2_550.2
IL10_HUMAN 296.9473975 FLNWIK_410.7_560.3 HABP2_HUMAN 282.9841332
LIENGYFHPVK_439.6_627.4 F13B_HUMAN 237.5320227 ECEELEEK_533.2_405.2
IL15_HUMAN 200.38281 FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN
194.6252869 QALEEFQK_496.8_680.3 CO8B_HUMAN 179.2518843
IIEVEEEQEDPYLNDR_996.0_777.4 FBLN1_HUMAN 177.7534111
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 164.9735228
ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN 162.2414693
LEEHYELR_363.5_580.3 PAI2_HUMAN 152.9262386
ISQGEADINIAFYQR_575.6_684.4 MMP8_HUMAN 144.2445011
HPWIVHWDQLPQYQLNR_744.0_918.5 KS6A3_HUMAN 140.2287926
AHYDLR_387.7_288.2 FETUA_HUMAN 137.9737525 GFQALGDAADIR_617.3_288.2
TIMP1_HUMAN 130.4945567 SWNEPLYHLVTEVR_581.6_716.4 PRL_HUMAN
127.442646 SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 120.5149446
YENYTSSFFIR_713.8_293.1 IL12B_HUMAN 117.0947487
FFQYDTWK_567.8_840.4 IGF2_HUMAN 109.8569617 HYFIAAVER_553.3_658.4
FA8_HUMAN 106.9426543 ITGFLKPGK_320.9_429.3 LBP_HUMAN 103.8056505
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 98.50490812
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 97.19989285 ALDLSLK_380.2_575.3
ITIH3_HUMAN 94.84900337 TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN
92.52335783 HPWIVHWDQLPQYQLNR_744.0_1047.0 KS6A3_HUMAN 91.77547608
LIQDAVTGLTVNGQITGDK_972.0_640.4 ITIH3_HUMAN 83.6483639
LNIGYIEDLK_589.3_837.4 PAI2_HUMAN 83.50221521
IALGGLLFPASNLR_481.3_657.4 SHBG_HUMAN 79.33146741
LPATEKPVLLSK_432.6_460.3 HYOU1_HUMAN 78.89429168
FQLSETNR_497.8_605.3 PSG2_HUMAN 78.13445824
NEIVFPAGILQAPFYTR_968.5_357.2 ECE1_HUMAN 75.12145257
ALDLSLK_380.2_185.1 ITIH3_HUMAN 63.05454715 DLHLSDVFLK_396.2_366.2
CO6_HUMAN 58.26831142 TQILEWAAER_608.8_761.4 EGLN_HUMAN 57.29461621
FSVVYAK_407.2_381.2 FETUA_HUMAN 54.78436389
VSEADSSNADWVTK_754.9_347.2 CFAB_HUMAN 54.40003244
DPNGLPPEAQK_583.3_669.4 RET4_HUMAN 53.89169348
VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN 53.33747599
LSSPAVITDK_515.8_830.5 PLMN_HUMAN 53.22513181
ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 51.5477235 AVLHIGEK_289.5_292.2
THBG_HUMAN 49.73092632 GEVTYTTSQVSK_650.3_750.4 EGLN_HUMAN
45.14743629 GYVIIKPLVWV_643.9_854.6 SAMP_HUMAN 44.05164273
TGVAVNKPAEFTVDAK_549.6_977.5 FLNA_HUMAN 42.99898046
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 42.90897411 ILDGGNK_358.7_490.2
CXCL5_HUMAN 42.60771281 FLPCENK_454.2_390.2 IL10_HUMAN 42.56799651
GFQALGDAADIR_617.3_717.4 TIMP1_HUMAN 38.68456017
SDGAKPGPR_442.7_213.6 COLI_HUMAN 38.47800265
NTGVISVVTTGLDR_716.4_662.4 CADH1_HUMAN 32.62953675
SERPPIFEIR_415.2_288.2 LRP1_HUMAN 31.48248968
DFHINLFQVLPWLK_885.5_400.2 CFAB_HUMAN 31.27286268
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 31.26972354
ELCLDPK_437.7_359.2 IL8_HUMAN 29.91108737 ILNIFGVIK_508.8_790.5
TFR1_HUMAN 29.88784921 TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3
ENPP2_HUMAN 29.42327998 GAVHVVVAETDYQSFAVLYLER_822.8_863.5
CO8G_HUMAN 26.70286929 AVLHIGEK_289.5_348.7 THBG_HUMAN 25.78703299
TFLTVYWTPER_706.9_401.2 ICAM1_HUMAN 24.73090242 AGITIPR_364.2_486.3
IL17_HUMAN 23.84580477 GAVHVVVAETDYQSFAVLYLER_822.8_580.3
CO8G_HUMAN 23.81167843 SLQAFVAVAAR_566.8_487.3 IL23A_HUMAN
23.61468839 SWNEPLYHLVTEVR_581.6_614.3 PRL_HUMAN 23.2538221
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 22.70115313
TAHISGLPPSTDFIVYLSGLAPSIR_871.5_800.5 TENA_HUMAN 22.42695892
QNYHQDSEAAINR_515.9_544.3 FRIH_HUMAN 21.96827269
AHQLAIDTYQEFEETYIPK_766.0_634.4 CSH_HUMAN 21.75765717
GDTYPAELYITGSILR_885.0_274.1 F13B_HUMAN 20.89751398
AHYDLR_387.7_566.3 FETUA_HUMAN 20.67629529
IALGGLLFPASNLR_481.3_412.3 SHBG_HUMAN 19.28973033
ATNATLDPR_479.8_272.2 PAR1_HUMAN 18.77604574 FSVVYAK_407.2_579.4
FETUA_HUMAN 17.81136564 HTLNQIDEVK_598.8_951.5 FETUA_HUMAN
17.29763288 DIPHWLNPTR_416.9_373.2 PAPP1_HUMAN 17.00562521
LYYGDDEK_501.7_563.2 CO8A_HUMAN 16.78897272
AALAAFNAQNNGSNFQLEEISR_789.1_633.3 FETUA_HUMAN 16.41986569
IQTHSTTYR_369.5_627.3 F13B_HUMAN 15.78335174
GPITSAAELNDPQSILLR_632.4_826.5 EGLN_HUMAN 15.3936876
QTLSWTVTPK_580.8_818.4 PZP_HUMAN 14.92509259
AVGYLITGYQR_620.8_737.4 PZP_HUMAN 13.9795325 DIIKPDPPK_511.8_342.2
IL12B_HUMAN 13.76508282 YNQLLR_403.7_288.2 ENOA_HUMAN 12.61733711
GNGLTWAEK_488.3_634.3 C163B_HUMAN 12.5891421 QVFAVQR_424.2_473.3
ELNE_HUMAN 12.57709327 FLQEQGHR_338.8_497.3 CO8G_HUMAN 12.51843475
HVVQLR_376.2_515.3 IL6RA_HUMAN 11.83747559
DVLLLVHNLPQNLTGHIWYK_791.8_883.0 PSG7_HUMAN 11.69074708
TFLTVYWTPER_706.9_502.3 ICAM1_HUMAN 11.63709776
VELAPLPSWQPVGK_760.9_400.3 ICAM1_HUMAN 10.79897269
TLFIFGVTK_513.3_215.1 PSG4_HUMAN 10.2831751 AYSDLSR_406.2_375.2
SAMP_HUMAN 10.00461148 HATLSLSIPR_365.6_472.3 VGFR3_HUMAN
9.967933028 LQGTLPVEAR_542.3_571.3 CO5_HUMAN 9.963760572
NTVISVNPSTK_580.3_732.4 VCAM1_HUMAN 9.124228658
EVFSKPISWEELLQ_852.9_260.2 FA40A_HUMAN 8.527980294
SLQNASAIESILK_687.4_860.5 IL3_HUMAN 8.429061621
IQHPFTVEEFVLPK_562.0_861.5 PZP_HUMAN 7.996504258
GVTGYFTFNLYLK_508.3_683.9 PSG5_HUMAN 7.94396229
VFQYIDLHQDEFVQTLK_708.4_361.2 CNDP1_HUMAN 7.860590049
ILDDLSPR_464.8_587.3 ITIH4_HUMAN 7.593889262
LIENGYFHPVK_439.6_343.2 F13B_HUMAN 7.05838337 VFQFLEK_455.8_811.4
CO5_HUMAN 6.976884759 AFTECCVVASQLR_770.9_574.3 CO5_HUMAN
6.847474286 WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 6.744837357
IQTHSTTYR_369.5_540.3 F13B_HUMAN 6.71464509 IAQYYYTFK_598.8_395.2
F13B_HUMAN 6.540497911 YGFYTHVFR_397.2_421.3 THRB_HUMAN 6.326347548
YHFEALADTGISSEFYDNANDLLSK_940.8_874.5 CO8A_HUMAN 6.261787525
ANDQYLTAAALHNLDEAVK_686.4_301.1 IL1A_HUMAN 6.217191651
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 6.1038295
GWVTDGFSSLK_598.8_854.4 APOC3_HUMAN 6.053494609
TLEAQLTPR_514.8_814.4 HEP2_HUMAN 5.855967278
VSAPSGTGHLPGLNPL_506.3_300.7 PSG3_HUMAN 5.625944609
EAQLPVIENK_570.8_699.4 PLMN_HUMAN 5.407703773
SPEAEDPLGVER_649.8_670.4 Z512B_HUMAN 5.341420139
IAIDLFK_410.3_635.4 HEP2_HUMAN 4.698739039
YEFLNGR_449.7_293.1 PLMN_HUMAN 4.658286706 VQTAHFK_277.5_502.3
CO8A_HUMAN 4.628247194 IEVIITLK_464.8_815.5 CXL11_HUMAN 4.57198762
ILTPEVR_414.3_601.3 GDF15_HUMAN 4.452884608 LEEHYELR_363.5_288.2
PAI2_HUMAN 4.411983862 HATLSLSIPR_365.6_272.2 VGFR3_HUMAN
4.334242077 NSDQEIDFK_548.3_294.2 S10A5_HUMAN 4.25302369
LPNNVLQEK_527.8_844.5 AFAM_HUMAN 4.183602548 ELANTIK_394.7_475.3
S10AC_HUMAN 4.13558153 LSIPQITTK_500.8_687.4 PSG5_HUMAN 3.966238797
TLNAYDHR_330.5_312.2 PAR3_HUMAN 3.961140111
WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN 3.941476057
ELLESYIDGR_597.8_710.4 THRB_HUMAN 3.832723338
ATLSAAPSNPR_542.8_570.3 CXCL2_HUMAN 3.82834767
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_598.4 SHBG_HUMAN 3.80737887
NADYSYSVWK_616.8_333.2 CO5_HUMAN 3.56404167 ILILPSVTR_506.3_559.3
PSGx_HUMAN 3.526998593 ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN
3.410412424 QVCADPSEEWVQK_788.4_275.2 CCL3_HUMAN 3.30795151
SVQNDSQAIAEVLNQLK_619.7_914.5 DESP_HUMAN 3.259270741
QVFAVQR_424.2_620.4 ELNE_HUMAN 3.211482663
ALPGEQQPLHALTR_511.0_807.5 IBP1_HUMAN 3.211207158
LEPLYSASGPGLRPLVIK_637.4_260.2 CAA60698 3.203088951
GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 3.139418139
DAGLSWGSAR_510.2_576.3 NEUR4_HUMAN 3.005197927
YGFYTHVFR_397.2_659.4 THRB_HUMAN 2.985663918
NNQLVAGYLQGPNVNLEEK_700.7_357.2 IL1RA_HUMAN 2.866983196
EKPAGGIPVLGSLVNTVLK_631.4_930.6 BPIB1_HUMAN 2.798965142
FGSDDEGR_441.7_735.3 PTHR_HUMAN 2.743283546
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 2.699725572
FATTFYQHLADSK_510.3_533.3 ANT3_HUMAN 2.615073729
DYWSTVK_449.7_347.2 APOC3_HUMAN 2.525459346
QLGLPGPPDVPDHAAYHPF_676.7_263.1 ITIH4_HUMAN 2.525383799
LSSPAVITDK_515.8_743.4 PLMN_HUMAN 2.522306831
TEFLSNYLTNVDDITLVPGTLGR_846.8_699.4 ENPP2_HUMAN 2.473366805
SILFLGK_389.2_201.1 THBG_HUMAN 2.472413913 VTFEYR_407.7_614.3
CRHBP_HUMAN 2.425338167 SVVLIPLGAVDDGEHSQNEK_703.0_798.4
CNDP1_HUMAN 2.421340244 HTLNQIDEVK_598.8_958.5 FETUA_HUMAN
2.419851187 ALNSIIDVYHK_424.9_661.3 S10A8_HUMAN 2.367904596
ETLALLSTHR_570.8_500.3 IL5_HUMAN 2.230076769
GLQYAAQEGLLALQSELLR_1037.1_858.5 LBP_HUMAN 2.205949216
TYNVDK_370.2_262.1 PPB1_HUMAN 2.11849772 FTITAGSK_412.7_576.3
FABPL_HUMAN 2.098589805 GIVEECCFR_585.3_900.3 IGF2_HUMAN
2.059942995 YGIEEHGK_311.5_599.3 CXA1_HUMAN 2.033828589
ALVLELAK_428.8_331.2 INHBE_HUMAN 1.993820617
ITLPDFTGDLR_624.3_920.5 LBP_HUMAN 1.968753183
HELTDEELQSLFTNFANVVDK_817.1_906.5 AFAM_HUMAN 1.916438806
EANQSTLENFLER_775.9_678.4 IL4_HUMAN 1.902033355
DADPDTFFAK_563.8_825.4 AFAM_HUMAN 1.882254674 LFIPQITR_494.3_727.4
PSG9_HUMAN 1.860649392 DPNGLPPEAQK_583.3_497.2 RET4_HUMAN
1.847702127 VEPLYELVTATDFAYSSTVR_754.4_549.3 CO8B_HUMAN 1.842159131
FQLSETNR_497.8_476.3 PSG2_HUMAN 1.834693717
FSLVSGWGQLLDR_493.3_516.3 FA7_HUMAN 1.790582748
NKPGVYTDVAYYLAWIR_677.0_545.3 FA12_HUMAN 1.777303353
FTGSQPFGQGVEHATANK_626.0_521.2 TSP1_HUMAN 1.736517431
DDLYVSDAFHK_655.3_704.3 ANT3_HUMAN 1.717534082
AFLEVNEEGSEAAASTAVVIAGR_764.4_685.4 ANT3_HUMAN 1.679420475
LPNNVLQEK_527.8_730.4 AFAM_HUMAN 1.66321148
IVLSLDVPIGLLQILLEQAR_735.1_503.3 UCN2_HUMAN 1.644983604
DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 1.625411496
SDLEVAHYK_531.3_617.3 CO8B_HUMAN 1.543640117
QLYGDTGVLGR_589.8_501.3 CO8G_HUMAN 1.505242962
VNHVTLSQPK_374.9_459.3 B2MG_HUMAN 1.48233058
TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 1.439531341
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 1.424401638 YGIEEHGK_311.5_341.2
CXA1_HUMAN 1.379872204 DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN
1.334272677 AEHPTWGDEQLFQTTR_639.3_569.3 PGH1_HUMAN 1.30549273
FQSVFTVTR_542.8_623.4 C1QC_HUMAN 1.302847429
VPGLYYFTYHASSR_554.3_420.2 C1QB_HUMAN 1.245565877
AYSDLSR_406.2_577.3 SAMP_HUMAN 1.220777002 ALEQDLPVNIK_620.4_570.4
CNDP1_HUMAN 1.216612522 NAVVQGLEQPHGLVVHPLR_688.4_890.6 LRP1_HUMAN
1.212935735 TSDQIHFFFAK_447.6_659.4 ANT3_HUMAN 1.176238265
GTYLYNDCPGPGQDTDCR_697.0_335.2 TNR1A_HUMAN 1.1455649
TSYQVYSK_488.2_787.4 C163A_HUMAN 1.048896429
ALNSIIDVYHK_424.9_774.4 S10A8_HUMAN 1.028522516
VELAPLPSWQPVGK_760.9_342.2 ICAM1_HUMAN 0.995831393
LSETNR_360.2_330.2 PSG1_HUMAN 0.976094717 HFQNLGK_422.2_527.2
AFAM_HUMAN 0.956286531 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN
0.947931674 LPATEKPVLLSK_432.6_347.2 HYOU1_HUMAN 0.932537153
SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN 0.905955419
DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 0.9032484 FFQYDTWK_567.8_712.3
IGF2_HUMAN 0.884340285 LIEIANHVDK_384.6_498.3 ADA12_HUMAN
0.881493383 AGFAGDDAPR_488.7_701.3 ACTB_HUMAN 0.814836556
YEFLNGR_449.7_606.3 PLMN_HUMAN 0.767373087 VIAVNEVGR_478.8_284.2
CHL1_HUMAN 0.721519592 SLSQQIENIR_594.3_531.3 CO1A1_HUMAN
0.712051082 EWVAIESDSVQPVPR_856.4_486.2 CNDP1_HUMAN 0.647712421
YGLVTYATYPK_638.3_843.4 CFAB_HUMAN 0.618499569
SVVLIPLGAVDDGEHSQNEK_703.0_286.2 CNDP1_HUMAN 0.606626346
NSDQEIDFK_548.3_409.2 S10A5_HUMAN 0.601928175
NVNQSLLELHK_432.2_543.3 FRIH_HUMAN 0.572008792
IAQYYYTFK_598.8_884.4 F13B_HUMAN 0.495062844
GPITSAAELNDPQSILLR_632.4_601.4 EGLN_HUMAN 0.47565795
YTTEIIK_434.2_704.4 C1R_HUMAN 0.433318952 GYVIIKPLVWV_643.9_304.2
SAMP_HUMAN 0.427905264 LDFHFSSDR_375.2_464.2 INHBC_HUMAN
0.411898116 IPSNPSHR_303.2_496.3 FBLN3_HUMAN 0.390037291
APLTKPLK_289.9_357.2 CRP_HUMAN 0.38859469
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.371359974
YENYTSSFFIR_713.8_756.4 IL12B_HUMAN 0.346336267 SPQAFYR_434.7_556.3
REL3_HUMAN 0.345901234 SVDEALR_395.2_488.3 PRDX2_HUMAN 0.307518869
FVFGTTPEDILR_697.9_742.4 TSP1_HUMAN 0.302313589
FTFTLHLETPKPSISSSNLNPR_829.4_787.4 PSG1_HUMAN 0.269826678
VGEYSLYIGR_578.8_708.4 SAMP_HUMAN 0.226573173 ILPSVPK_377.2_244.2
PGH1_HUMAN 0.225429414 LFIPQITR_494.3_614.4 PSG9_HUMAN 0.18285533
TGYYFDGISR_589.8_857.4 FBLN1_HUMAN 0.182474114
HYGGLTGLNK_530.3_759.4 PGAM1_HUMAN 0.152397007
NQSPVLEPVGR_598.3_866.5 KS6A3_HUMAN 0.128963949
IGKPAPDFK_324.9_294.2 PRDX2_HUMAN 0.113383235
TSESTGSLPSPFLR_739.9_716.4 PSMG1_HUMAN 0.108159874
ESDTSYVSLK_564.8_347.2 CRP_HUMAN 0.08569303
ETPEGAEAKPWYEPIYLGGVFQLEK_951.1_877.5 TNFA_HUMAN 0.039781728
TSDQIHFFFAK_447.6_512.3 ANT3_HUMAN 0.008064465
TABLE-US-00022 TABLE 21 Lasso32 Middle Window Co- effi- Variable
UniProt_ID cient SEYGAALAWEK_612.8_788.4 CO6_HUMAN 6.99
VFQFLEK_455.8_811.4 CO5_HUMAN 6.43 VLEPTLK_400.3_458.3 VTDB_HUMAN
3.99 SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 3.33 TLAFVR_353.7_492.3
FA7_HUMAN 2.44 YGIEEHGK_311.5_599.3 CXA1_HUMAN 2.27
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 2.14
QGHNSVFLIK_381.6_520.4 HEMO_HUMAN 0.25
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -2.81
ELPQSIVYK_538.8_417.7 FBLN3_HUMAN -3.46 VNHVTLSQPK_374.9_244.2
B2MG_HUMAN -6.61
TABLE-US-00023 TABLE 22 Lasso100 Middle Window Co- effi- Variable
UniProt_ID cient VFQFLEK_455.8_811.4 CO5_HUMAN 6.89
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 4.67 GEVTYTTSQVSK_650.3_750.4
EGLN_HUMAN 3.4 QVFAVQR_424.2_473.3 ELNE_HUMAN 1.94
VELAPLPSWQPVGK_760.9_342.2 ICAM1_HUMAN 1.91
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 1.8
SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 1.67 YGIEEHGK_311.5_599.3
CXA1_HUMAN 1.53 YGIEEHGK_311.5_341.2 CXA1_HUMAN 1.51
HYINLITR_515.3_301.1 NPY_HUMAN 1.47 TLAFVR_353.7_492.3 FA7_HUMAN
1.46 GVTGYFTFNLYLK_508.3_260.2 PSG5_HUMAN 1.28
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 0.84
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.41
VELAPLPSWQPVGK_760.9_400.3 ICAM1_HUMAN 0.3
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN -0.95 ELPQSIVYK_538.8_417.7
FBLN3_HUMAN -1.54 DVLLLVHNLPQNLTGHIWYK_791.8_310.2 PSG7_HUMAN -1.54
VPLALFALNR_557.3_620.4 PEPD_HUMAN -1.91
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -2.3
VNHVTLSQPK_374.9_244.2 B2MG_HUMAN -3.6 EVFSKPISWEELLQ_852.9_376.2
FA40A_HUMAN -3.96
TABLE-US-00024 TABLE 23 Lasso Protein Middle Window Co- effi-
Variable UniProt_ID cient SEYGAALAWEK_612.8_788.4 CO6_HUMAN 5.84
VFQFLEK_455.8_811.4 CO5_HUMAN 5.58 SLDFTELDVAAEK_719.4_316.2
ANGT_HUMAN 2.11 TLAFVR_353.7_492.3 FA7_HUMAN 1.83
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 1.62 HYINLITR_515.3_301.1
NPY_HUMAN 1.39 VLEPTLK_400.3_458.3 VTDB_HUMAN 1.37
YGIEEHGK_311.5_599.3 CXA1_HUMAN 1.17 VELAPLPSWQPVGK_760.9_342.2
ICAM1_HUMAN 1.13 QVFAVQR_424.2_473.3 ELNE_HUMAN 0.79
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.23
DVLLLVHNLPQNLTGHIWYK_791.8_310.2 PSG7_HUMAN -0.61
VEHSDLSFSK_383.5_234.1 B2MG_HUMAN -0.69 AVDIPGLEAATPYR_736.9_399.2
TENA_HUMAN -0.85 VPLALFALNR_557.3_620.4 PEPD_HUMAN -1.45
ELPQSIVYK_538.8_417.7 FBLN3_HUMAN -1.9
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -2.07
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN -2.32
TABLE-US-00025 TABLE 24 Lasso All Middle Window Co- effi- Variable
UniProt_ID cient SEYGAALAWEK_612.8_788.4 CO6_HUMAN 2.48
VFQFLEK_455.8_811.4 CO5_HUMAN 2.41 SLDFTELDVAAEK_719.4_316.2
ANGT_HUMAN 1.07 YGIEEHGK_311.5_599.3 CXA1_HUMAN 0.64
VLEPTLK_400.3_458.3 VTDB_HUMAN 0.58 LHEAFSPVSYQHDLALLR_699.4_251.2
FA12_HUMAN 0.21 LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -0.62
VNHVTLSQPK_374.9_244.2 B2MG_HUMAN -1.28
TABLE-US-00026 TABLE 25 Lasso32 Middle-Late Window Variable
UniProt_ID Coefficient SEYGAALAWEK_612.8_845.5 CO6_HUMAN 4.35
TLAFVR_353.7_492.3 FA7_HUMAN 2.42 YGIEEHGK_311.5_599.3 CXA1_HUMAN
1.46 DFNQFSSGEK_386.8_333.2 FETA_HUMAN 1.37 VFQFLEK_455.8_811.4
CO5_HUMAN 0.89 LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.85
QINSYVK_426.2_496.3 CBG_HUMAN 0.56 TYLHTYESEI_628.3_515.3
ENPP2_HUMAN 0.53 SLQAFVAVAAR_566.8_804.5 IL23A_HUMAN 0.39
TEQAAVAR_423.2_615.4 FA12_HUMAN 0.26 VLEPTLK_400.3_587.3 VTDB_HUMAN
0.24 AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN -2.08
VPLALFALNR_557.3_620.4 PEPD_HUMAN -2.09 AVYEAVLR_460.8_587.4
PEPD_HUMAN -3.37
TABLE-US-00027 TABLE 26 Lasso100 Middle-Late Window Variable
UniProt_ID Coefficient VFQFLEK_455.8_811.4 CO5_HUMAN 3.82
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 2.94 YGIEEHGK_311.5_599.3
CXA1_HUMAN 2.39 DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 2.05
TLAFVR_353.7_492.3 FA7_HUMAN 1.9 NQSPVLEPVGR_598.3_866.5
KS6A3_HUMAN 1.87 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 1.4
TQILEWAAER_608.8_761.4 EGLN_HUMAN 1.29 VVGGLVALR_442.3_784.5
FA12_HUMAN 1.24 QINSYVK_426.2_496.3 CBG_HUMAN 1.14
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.84 ALEQDLPVNIK_620.4_570.4
CNDP1_HUMAN 0.74 GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.51
SLQNASAIESILK_687.4_860.5 IL3_HUMAN 0.44 DLHLSDVFLK_396.2_260.2
CO6_HUMAN 0.38 LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.37
NIQSVNVK_451.3_674.4 GROA_HUMAN 0.3 FFQYDTWK_567.8_712.3 IGF2_HUMAN
0.19 ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.19
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.15
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN -0.09
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN -0.52
TSYQVYSK_488.2_787.4 C163A_HUMAN -0.62 AVDIPGLEAATPYR_736.9_399.2
TENA_HUMAN -1.29 TAHISGLPPSTDFIVYLSGLAPSIR_871.5_472.3 TENA_HUMAN
-1.53 AEIEYLEK_497.8_552.3 LYAM1_HUMAN -1.73
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -1.95
VPLALFALNR_557.3_620.4 PEPD_HUMAN -2.9 AVYEAVLR_460.8_587.4
PEPD_HUMAN -3.04 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN -3.49
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN -3.71
TABLE-US-00028 TABLE 27 Lasso Protein Middle-LateWindow Variable
UniProt_ID Coefficient VFQFLEK_455.8_811.4 CO5_HUMAN 4.25
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 3.06 YGIEEHGK_311.5_599.3
CXA1_HUMAN 2.36 SEPRPGVLLR_375.2_654.4 FA7_HUMAN 2.11
TQILEWAAER_608.8_761.4 EGLN_HUMAN 1.81 NQSPVLEPVGR_598.3_866.5
KS6A3_HUMAN 1.79 TEQAAVAR_423.2_615.4 FA12_HUMAN 1.72
QINSYVK_426.2_496.3 CBG_HUMAN 0.98 ALEQDLPVNIK_620.4_570.4
CNDP1_HUMAN 0.98 NCSFSIIYPVVIK_770.4_555.4 CRHBP_HUMAN 0.76
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.63 SLQNASAIESILK_687.4_860.5
IL3_HUMAN 0.59 ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.55
GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.55
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.46 NIQSVNVK_451.3_674.4
GROA_HUMAN 0.22 LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.11
FFQYDTWK_567.8_712.3 IGF2_HUMAN 0.01 TSYQVYSK_488.2_787.4
C163A_HUMAN -0.76 AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN
-1.31 AEIEYLEK_497.8_552.3 LYAM1_HUMAN -1.59
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -1.73
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN -2.02
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN -3
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN -3.15 ELPQSIVYK_538.8_417.7
FBLN3_HUMAN -3.49 VNHVTLSQPK_374.9_244.2 B2MG_HUMAN -3.82
VPLALFALNR_557.3_620.4 PEPD_HUMAN -4.94
TABLE-US-00029 TABLE 28 Lasso All Middle-LateWindow Variable
UniProt_ID Coefficient ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 2.38
TLAFVR_353.7_492.3 FA7_HUMAN 0.96 YGIEEHGK_311.5_599.3 CXA1_HUMAN
0.34 DPTFIPAPIQAK_433.2_461.2 ANGT_HUMAN 0.33
DFNQFSSGEK_386.8_333.2 FETA_HUMAN 0.13 QINSYVK_426.2_496.3
CBG_HUMAN 0.03 TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN -0.02
AEIEYLEK_497.8_552.3 LYAM1_HUMAN -0.05 VNHVTLSQPK_374.9_244.2
B2MG_HUMAN -0.12 LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN -0.17
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN -0.31
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN -0.35 VPLALFALNR_557.3_620.4
PEPD_HUMAN -0.43 AVYEAVLR_460.8_587.4 PEPD_HUMAN -2.33
TABLE-US-00030 TABLE 29 Lasso 32 LateWindow Variable UniProt_ID
Coefficient QINSYVK_426.2_610.3 CBG_HUMAN 3.24 ILDGGNK_358.7_603.3
CXCL5_HUMAN 2.65 VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN 2.55
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 2.12 YSHYNER_323.5_418.2
HABP2_HUMAN 1.63 DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 1.22
SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 0.96 FGFGGSTDSGPIR_649.3_745.4
ADA12_HUMAN 0.86 GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.45
TSYQVYSK_488.2_787.4 C163A_HUMAN -1.73 TGVAVNKPAEFTVDAK_549.6_258.1
FLNA_HUMAN -2.56 SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN -3.04
VPLALFALNR_557.3_620.4 PEPD_HUMAN -3.33 YYGYTGAFR_549.3_450.3
TRFL_HUMAN -4.24 AVYEAVLR_460.8_587.4 PEPD_HUMAN -5.83
AEIEYLEK_497.8_552.3 LYAM1_HUMAN -6.52
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN -6.55
TABLE-US-00031 TABLE 30 Lasso 100 Late Window Variable UniProt_ID
Coefficient SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 4.13
ILDGGNK_358.7_603.3 CXCL5_HUMAN 3.57 QINSYVK_426.2_610.3 CBG_HUMAN
3.41 DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 1.64
VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN 1.57
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 1.45 LTTVDIVTLR_565.8_815.5
IL2RB_HUMAN 0.71 YSHYNER_323.5_418.2 HABP2_HUMAN 0.68
FFQYDTWK_567.8_712.3 IGF2_HUMAN 0.42
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 0.36
GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.21
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.1 VGVISFAQK_474.8_580.3
TFR2_HUMAN 0.08 TSYQVYSK_488.2_787.4 C163A_HUMAN -0.36
ALNFGGIGVVVGHELTHAFDDQGR_837.1_360.2 ECE1_HUMAN -0.65
AYSDLSR_406.2_375.2 SAMP_HUMAN -1.23 TGVAVNKPAEFTVDAK_549.6_258.1
FLNA_HUMAN -1.63 SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN -2.29
YYGYTGAFR_549.3_450.3 TRFL_HUMAN -2.58 VPLALFALNR_557.3_620.4
PEPD_HUMAN -2.73 YISPDQLADLYK_713.4_277.2 ENOA_HUMAN -2.87
AVDIPGLEAATPYR_736.9_286.1 TENA_HUMAN -3.9 AEIEYLEK_497.8_552.3
LYAM1_HUMAN -5.29 AVYEAVLR_460.8_587.4 PEPD_HUMAN -5.51
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN -6.49
TABLE-US-00032 TABLE 31 Lasso Protein Late Window Variable
UniProt_ID Coefficient SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 3.33
ILDGGNK_358.7_603.3 CXCL5_HUMAN 3.25 QINSYVK_426.2_496.3 CBG_HUMAN
2.41 YSHYNER_323.5_418.2 HABP2_HUMAN 1.82 ALEQDLPVNIK_620.4_798.5
CNDP1_HUMAN 1.32 LIEIANHVDK_384.6_683.4 ADA12_HUMAN 1.27
GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.26
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 0.18
LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.18 TSYQVYSK_488.2_787.4
C163A_HUMAN -0.11 TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN -0.89
AYSDLSR_406.2_375.2 SAMP_HUMAN -1.47 SPEAEDPLGVER_649.8_314.1
Z512B_HUMAN -1.79 YYGYTGAFR_549.3_450.3 TRFL_HUMAN -2.22
YISPDQLADLYK_713.4_277.2 ENOA_HUMAN -2.41
AVDIPGLEAATPYR_736.9_286.1 TENA_HUMAN -2.94 AEIEYLEK_497.8_552.3
LYAM1_HUMAN -5.18 AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN
-5.71 AVYEAVLR_460.8_587.4 PEPD_HUMAN -7.33
TABLE-US-00033 TABLE 32 Lasso All Late Window Variable UniProt_ID
Coefficient QINSYVK_426.2_496.3 CBG_HUMAN 0.5
DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 0.15 ALEQDLPVNIK_620.4_570.4
CNDP1_HUMAN 0.11 ILDGGNK_358.7_603.3 CXCL5_HUMAN 0.08
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.06 YYGYTGAFR_549.3_450.3
TRFL_HUMAN -0.39 AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN
-1.57 AEIEYLEK_497.8_552.3 LYAM1_HUMAN -2.46 AVYEAVLR_460.8_587.4
PEPD_HUMAN -2.92
TABLE-US-00034 TABLE 33 Random Forest 32 Early Window Variable
Protein MeanDecreaseGini ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN
3.224369171 AHYDLR_387.7_288.2 FETUA_HUMAN 1.869007658
FSVVYAK_407.2_381.2 FETUA_HUMAN 1.770198171 ITLPDFTGDLR_624.3_288.2
LBP_HUMAN 1.710936472 ITGFLKPGK_320.9_301.2 LBP_HUMAN 1.623922439
ITGFLKPGK_320.9_429.3 LBP_HUMAN 1.408035272
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 1.345412168
VFQFLEK_455.8_811.4 CO5_HUMAN 1.311332013 VQTAHFK_277.5_431.2
CO8A_HUMAN 1.308902373 FLNWIK_410.7_560.3 HABP2_HUMAN 1.308093745
DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN 1.297033607
TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 1.291280928
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 1.28622301
QALEEFQK_496.8_680.3 CO8B_HUMAN 1.191731825 FSVVYAK_407.2_579.4
FETUA_HUMAN 1.078909138 ITLPDFTGDLR_624.3_920.5 LBP_HUMAN
1.072613747 AHYDLR_387.7_566.3 FETUA_HUMAN 1.029562263
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 1.00992071
DVLLLVHNLPQNLPGYFWYK_810.4_967.5 PSG9_HUMAN 1.007095529
SFRPFVPR_335.9_635.3 LBP_HUMAN 0.970312536 SDLEVAHYK_531.3_617.3
CO8B_HUMAN 0.967904893 VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN
0.960398254 VFQFLEK_455.8_276.2 CO5_HUMAN 0.931652095
SLLQPNK_400.2_599.4 CO8A_HUMAN 0.926470249 SFRPFVPR_335.9_272.2
LBP_HUMAN 0.911599611 FLNWIK_410.7_561.3 HABP2_HUMAN 0.852022868
LSSPAVITDK_515.8_743.4 PLMN_HUMAN 0.825455824
DVLLLVHNLPQNLPGYFWYK_810.4_594.3 PSG9_HUMAN 0.756797142
ALVLELAK_428.8_672.4 INHBE_HUMAN 0.748802555 DISEVVTPR_508.3_787.4
CFAB_HUMAN 0.733731518
TABLE-US-00035 TABLE 34 Random Forest 100 Early Window Variable
Protein MeanDecreaseGini ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN
1.709778508 LPNNVLQEK_527.8_844.5 AFAM_HUMAN 0.961692716
AHYDLR_387.7_288.2 FETUA_HUMAN 0.901586746 ITLPDFTGDLR_624.3_288.2
LBP_HUMAN 0.879119498 IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN
0.842483095 ITGFLKPGK_320.9_301.2 LBP_HUMAN 0.806905233
FSVVYAK_407.2_381.2 FETUA_HUMAN 0.790429706 ITGFLKPGK_320.9_429.3
LBP_HUMAN 0.710312386 VFQFLEK_455.8_811.4 CO5_HUMAN 0.709531553
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 0.624325189
DADPDTFFAK_563.8_825.4 AFAM_HUMAN 0.618684313 FLNWIK_410.7_560.3
HABP2_HUMAN 0.617501242 TASDFITK_441.7_781.4 GELS_HUMAN 0.609275999
DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN 0.588718595 VQTAHFK_277.5_431.2
CO8A_HUMAN 0.58669845 TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 0.5670608
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 0.555624783
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 0.537678415 HFQNLGK_422.2_527.2
AFAM_HUMAN 0.535543137 TASDFITK_441.7_710.4 GELS_HUMAN 0.532743323
ITLPDFTGDLR_624.3_920.5 LBP_HUMAN 0.51667902 QALEEFQK_496.8_680.3
CO8B_HUMAN 0.511314017 AVLHIGEK_289.5_348.7 THBG_HUMAN 0.510284122
FSVVYAK_407.2_579.4 FETUA_HUMAN 0.503907813 LPNNVLQEK_527.8_730.4
AFAM_HUMAN 0.501281631 AHYDLR_387.7_566.3 FETUA_HUMAN 0.474166711
IAPQLSTEELVSLGEK_857.5_333.2 AFAM_HUMAN 0.459595701
WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 0.44680777
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.434157773
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.432484862
TABLE-US-00036 TABLE 35 Random Forest Protein Early Window Variable
Protein MeanDecreaseGini ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN
2.881452809 LPNNVLQEK_527.8_844.5 AFAM_HUMAN 1.833987752
ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 1.608843881
IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN 1.594658208
VFQFLEK_455.8_811.4 CO5_HUMAN 1.290134412
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN 1.167981736
TASDFITK_441.7_781.4 GELS_HUMAN 1.152847453 DAGLSWGSAR_510.3_390.2
NEUR4_HUMAN 1.146752656 FSVVYAK_407.2_579.4 FETUA_HUMAN 1.060168583
AVLHIGEK_289.5_348.7 THBG_HUMAN 1.033625773 FLNWIK_410.7_560.3
HABP2_HUMAN 1.022356789 QALEEFQK_496.8_680.3 CO8B_HUMAN 0.990074129
DVLLLVHNLPQNLPGYFWYK_810.4_967.5 PSG9_HUMAN 0.929633865
WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 0.905895642
VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN 0.883887371
NNQLVAGYLQGPNVNLEEK_700.7_999.5 IL1RA_HUMAN 0.806472085
SLLQPNK_400.2_599.4 CO8A_HUMAN 0.783623222
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 0.774365756
NIQSVNVK_451.3_674.4 GROA_HUMAN 0.767963386
HPWIVHWDQLPQYQLNR_744.0_1047.0 KS6A3_HUMAN 0.759960139
TTSDGGYSFK_531.7_860.4 INHA_HUMAN 0.732813448
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.718779092
LSSPAVITDK_515.8_743.4 PLMN_HUMAN 0.699547739
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.693159192
TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.647300964 DISEVVTPR_508.3_787.4
CFAB_HUMAN 0.609165621 LIENGYFHPVK_439.6_627.4 F13B_HUMAN
0.60043345 SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 0.596079858
ALQDQLVLVAAK_634.9_289.2 ANGT_HUMAN 0.579034994
ALVLELAK_428.8_672.4 INHBE_HUMAN 0.573458483
TABLE-US-00037 TABLE 36 Random Forest All Early Window Variable
Protein MeanDecreaseGini ELIEELVNITQNQK_557.6_517.3 IL13_HUMAN
0.730972421 ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 0.409808774
AHYDLR_387.7_288.2 FETUA_HUMAN 0.409298983 FSVVYAK_407.2_381.2
FETUA_HUMAN 0.367730833 ITGFLKPGK_320.9_301.2 LBP_HUMAN 0.350485117
VFQFLEK_455.8_811.4 CO5_HUMAN 0.339289475
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 0.334303166
LPNNVLQEK_527.8_844.5 AFAM_HUMAN 0.329800706
IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN 0.325596677
ITGFLKPGK_320.9_429.3 LBP_HUMAN 0.31473104 FLNWIK_410.7_560.3
HABP2_HUMAN 0.299810081 LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN
0.295613448 ITLPDFTGDLR_624.3_920.5 LBP_HUMAN 0.292212699
DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN 0.285812225
TLLPVSKPEIR_418.3_288.2 CO5_HUMAN 0.280857718 FSVVYAK_407.2_579.4
FETUA_HUMAN 0.278531322 DADPDTFFAK_563.8_825.4 AFAM_HUMAN
0.258938798 AHYDLR_387.7_566.3 FETUA_HUMAN 0.256160046
QALEEFQK_496.8_680.3 CO8B_HUMAN 0.245543641 HTLNQIDEVK_598.8_951.5
FETUA_HUMAN 0.239528081 TASDFITK_441.7_781.4 GELS_HUMAN 0.227485958
VFQFLEK_455.8_276.2 CO5_HUMAN 0.226172392
DVLLLVHNLPQNLPGYFWYK_810.4_967.5 PSG9_HUMAN 0.218613384
VQTAHFK_277.5_431.2 CO8A_HUMAN 0.217171548 SFRPFVPR_335.9_635.3
LBP_HUMAN 0.214798112 HFQNLGK_422.2_527.2 AFAM_HUMAN 0.211756476
SVSLPSLDPASAK_636.4_473.3 APOB_HUMAN 0.211319422
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.206574494
HFQNLGK_422.2_285.1 AFAM_HUMAN 0.204024196 AVLHIGEK_289.5_348.7
THBG_HUMAN 0.201102917
TABLE-US-00038 TABLE 37 Random Forest SummedGini Early Window
Transition Protein SumBestGini ELIEELVNITQNQK_557.6_517.3
IL13_HUMAN 242.5373659 VFQFLEK_455.8_811.4 CO5_HUMAN 115.1113943
FLNWIK_410.7_560.3 HABP2_HUMAN 107.4572447 ITLPDFTGDLR_624.3_288.2
LBP_HUMAN 104.0742727 LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN
103.3238077 DAGLSWGSAR_510.3_390.2 NEUR4_HUMAN 70.4151533
AHYDLR_387.7_288.2 FETUA_HUMAN 140.2670822 FSVVYAK_407.2_381.2
FETUA_HUMAN 121.3664352 LPNNVLQEK_527.8_844.5 AFAM_HUMAN
115.5211679 ITGFLKPGK_320.9_429.3 LBP_HUMAN 114.9512704
ITGFLKPGK_320.9_301.2 LBP_HUMAN 112.916627
IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN 52.21169288
VQTAHFK_277.5_431.2 CO8A_HUMAN 144.5237215 TLLPVSKPEIR_418.3_288.2
CO5_HUMAN 96.16982897 QALEEFQK_496.8_680.3 CO8B_HUMAN 85.35050759
FSVVYAK_407.2_579.4 FETUA_HUMAN 73.23969945
ELIEELVNITQNQK_557.6_618.3 IL13_HUMAN 61.61450671
TASDFITK_441.7_781.4 GELS_HUMAN 61.32155633
DVLLLVHNLPQNLPGYFWYK_810.4_967.5 PSG9_HUMAN 99.68404123
AVLHIGEK_289.5_348.7 THBG_HUMAN 69.96748485 ITLPDFTGDLR_624.3_920.5
LBP_HUMAN 56.66810872 WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN
56.54173176 VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN 47.92505575
DADPDTFFAK_563.8_825.4 AFAM_HUMAN 40.34147696
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 145.0311483
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 109.4072996
FLPCENK_454.2_550.2 IL10_HUMAN 105.7756691 VQTAHFK_277.5_502.3
CO8A_HUMAN 101.5877845 VFQFLEK_455.8_276.2 CO5_HUMAN 95.71159157
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 94.92157517
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 90.67568777
NKPGVYTDVAYYLAWIR_677.0_545.3 FA12_HUMAN 90.35890105
LEEHYELR_363.5_580.3 PAI2_HUMAN 88.44833508
HPWIVHWDQLPQYQLNR_744.0_1047.0 KS6A3_HUMAN 88.37680942
HTLNQIDEVK_598.8_951.5 FETUA_HUMAN 87.63064143
LPNNVLQEK_527.8_730.4 AFAM_HUMAN 86.64484642 ALDLSLK_380.2_575.3
ITIH3_HUMAN 83.51201287 YGIEEHGK_311.5_599.3 CXA1_HUMAN 82.47620831
LSSPAVITDK_515.8_830.5 PLMN_HUMAN 81.5433587 LEEHYELR_363.5_288.2
PAI2_HUMAN 79.01571985 NVIQISNDLENLR_509.9_402.3 LEP_HUMAN
78.86670236 SGFSFGFK_438.7_732.4 CO8B_HUMAN 78.71961929
SDLEVAHYK_531.3_617.3 CO8B_HUMAN 78.24005567 NADYSYSVWK_616.8_333.2
CO5_HUMAN 76.07974354 AHYDLR_387.7_566.3 FETUA_HUMAN 74.68253347
GAVHVVVAETDYQSFAVLYLER_822.8_580.3 CO8G_HUMAN 73.75860248
LIENGYFHPVK_439.6_627.4 F13B_HUMAN 73.74965194 ALDLSLK_380.2_185.1
ITIH3_HUMAN 72.760739 WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN
72.51936706 FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 72.49183198
GLQYAAQEGLLALQSELLR_1037.1_929.5 LBP_HUMAN 67.17588648
HFQNLGK_422.2_527.2 AFAM_HUMAN 66.11702719 YSHYNER_323.5_581.3
HABP2_HUMAN 65.56238612 ISQGEADINIAFYQR_575.6_684.4 MMP8_HUMAN
65.50301246 TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 64.85259525
NIQSVNVK_451.3_674.4 GROA_HUMAN 64.53010225
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 64.12149927
SLLQPNK_400.2_599.4 CO8A_HUMAN 62.68167847 SFRPFVPR_335.9_635.3
LBP_HUMAN 61.90157662 NNQLVAGYLQGPNVNLEEK_700.7_999.5 IL1RA_HUMAN
61.54435815 LYYGDDEK_501.7_563.2 CO8A_HUMAN 60.16700473
SWNEPLYHLVTEVR_581.6_716.4 PRL_HUMAN 59.78209065
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 58.93982896
GTYLYNDCPGPGQDTDCR_697.0_335.2 TNR1A_HUMAN 58.72963941
HATLSLSIPR_365.6_472.3 VGFR3_HUMAN 57.98669834 FIVGFTR_420.2_261.2
CCL20_HUMAN 57.23165578 QNYHQDSEAAINR_515.9_544.3 FRIH_HUMAN
57.21116697 DVLLLVHNLPQNLPGYFWYK_810.4_594.3 PSG9_HUMAN 56.84150484
FLNWIK_410.7_561.3 HABP2_HUMAN 56.37258274 SLQAFVAVAAR_566.8_487.3
IL23A_HUMAN 56.09012981 HFQNLGK_422.2_285.1 AFAM_HUMAN 56.04480022
GPGEDFR_389.2_322.2 PTGDS_HUMAN 55.7583763
NKPGVYTDVAYYLAWIR_677.0_821.5 FA12_HUMAN 55.53857645
LIQDAVTGLTVNGQITGDK_972.0_640.4 ITIH3_HUMAN 55.52577583
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 54.27147366 TLNAYDHR_330.5_312.2
PAR3_HUMAN 54.19190934 IQTHSTTYR_369.5_627.3 F13B_HUMAN 54.18950583
TASDFITK_441.7_710.4 GELS_HUMAN 54.1056456
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 53.8997252
DADPDTFFAK_563.8_302.1 AFAM_HUMAN 53.85914848
SVSLPSLDPASAK_636.4_473.3 APOB_HUMAN 53.41996191
TTSDGGYSFK_531.7_860.4 INHA_HUMAN 52.24655536
AFTECCVVASQLR_770.9_574.3 CO5_HUMAN 51.67853429
ELPQSIVYK_538.8_409.2 FBLN3_HUMAN 51.35853002
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 51.23842124 FQLSETNR_497.8_605.3
PSG2_HUMAN 51.01576848 GSLVQASEANLQAAQDFVR_668.7_806.4 ITIH1_HUMAN
50.81923338 FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 50.54425114
ECEELEEK_533.2_405.2 IL15_HUMAN 50.41977421 NADYSYSVWK_616.8_769.4
CO5_HUMAN 50.36434595 SLLQPNK_400.2_358.2 CO8A_HUMAN 49.75593162
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 49.43389721
DISEVVTPR_508.3_787.4 CFAB_HUMAN 49.00234897
AEVIWTSSDHQVLSGK_586.3_300.2 PD1L1_HUMAN 48.79028835
SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 48.70665587 SILFLGK_389.2_201.1
THBG_HUMAN 48.5997957 AVLHIGEK_289.5_292.2 THBG_HUMAN 48.4605866
QLYGDTGVLGR_589.8_501.3 CO8G_HUMAN 48.11414904
FSLVSGWGQLLDR_493.3_516.3 FA7_HUMAN 47.59635333
DSPVLIDFFEDTER_841.9_399.2 HRG_HUMAN 46.83840473
INPASLDK_429.2_630.4 C163A_HUMAN 46.78947931
GAVHVVVAETDYQSFAVLYLER_822.8_863.5 CO8G_HUMAN 46.66185339
FLQEQGHR_338.8_497.3 CO8G_HUMAN 46.64415952 LNIGYIEDLK_589.3_837.4
PAI2_HUMAN 46.5879123 LSSPAVITDK_515.8_743.4 PLMN_HUMAN 46.2857838
GLQYAAQEGLLALQSELLR_1037.1_858.5 LBP_HUMAN 45.7427767
SDGAKPGPR_442.7_213.6 COLI_HUMAN 45.27828366 GYQELLEK_490.3_502.3
FETA_HUMAN 43.52928868 GGEGTGYFVDFSVR_745.9_869.5 HRG_HUMAN
43.24514327 ADLFYDVEALDLESPK_913.0_447.2 HRG_HUMAN 42.56268679
ADLFYDVEALDLESPK_913.0_331.2 HRG_HUMAN 42.48967422
EAQLPVIENK_570.8_699.4 PLMN_HUMAN 42.21213429 SILFLGK_389.2_577.4
THBG_HUMAN 42.03379581 HTLNQIDEVK_598.8_958.5 FETUA_HUMAN
41.98377176 AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN
41.89547273 FLPCENK_454.2_390.2 IL10_HUMAN 41.66612478
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 41.50878046
DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 41.27830935
SLQAFVAVAAR_566.8_804.5 IL23A_HUMAN 41.00430596
YISPDQLADLYK_713.4_277.2 ENOA_HUMAN 40.90053801
SLPVSDSVLSGFEQR_810.9_836.4 CO8G_HUMAN 40.62020941
DGSPDVTTADIGANTPDATK_973.5_531.3 PGRP2_HUMAN 40.33913091
NTGVISVVTTGLDR_716.4_662.4 CADH1_HUMAN 40.05291612
ALVLELAK_428.8_672.4 INHBE_HUMAN 40.01646465 YEFLNGR_449.7_293.1
PLMN_HUMAN 39.83344278 WGAAPYR_410.7_577.3 PGRP2_HUMAN 39.52766213
TFLTVYWTPER_706.9_401.2 ICAM1_HUMAN 39.13662034
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 38.77511119 VGVISFAQK_474.8_693.4
TFR2_HUMAN 38.5823457 IIEVEEEQEDPYLNDR_996.0_777.4 FBLN1_HUMAN
38.30913304 TGYYFDGISR_589.8_694.4 FBLN1_HUMAN 38.30617106
LQGTLPVEAR_542.3_571.3 CO5_HUMAN 37.93064544
DSPVLIDFFEDTER_841.9_512.3 HRG_HUMAN 37.4447737
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 37.02483715
DGSPDVTTADIGANTPDATK_973.5_844.4 PGRP2_HUMAN 36.59864788
ILILPSVTR_506.3_785.5 PSGx_HUMAN 36.43814815
SVSLPSLDPASAK_636.4_885.5 APOB_HUMAN 36.27689491 TLAFVR_353.7_492.3
FA7_HUMAN 36.18771771 VAPGVANPGTPLA_582.3_555.3 A6NIT4_HUMAN
35.70677357 HELTDEELQSLFTNFANVVDK_817.1_906.5 AFAM_HUMAN
35.14441609 AGLLRPDYALLGHR_518.0_369.2 PGRP2_HUMAN 35.13047098
GDTYPAELYITGSILR_885.0_1332.8 F13B_HUMAN 34.97832404
LFIPQITR_494.3_727.4 PSG9_HUMAN 34.76811249 GYQELLEK_490.3_631.4
FETA_HUMAN 34.76117605 VSEADSSNADWVTK_754.9_533.3 CFAB_HUMAN
34.49787512 LNIGYIEDLK_589.3_950.5 PAI2_HUMAN 34.48448691
SFRPFVPR_335.9_272.2 LBP_HUMAN 34.27529415 ILDGGNK_358.7_490.2
CXCL5_HUMAN 34.2331388 EANQSTLENFLER_775.9_678.4 IL4_HUMAN
34.14295797 DFNQFSSGEK_386.8_189.1 FETA_HUMAN 34.05459951
IEEIAAK_387.2_660.4 CO5_HUMAN 33.93778148
TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN 33.87864446
LPATEKPVLLSK_432.6_347.2 HYOU1_HUMAN 33.69005522
FLQEQGHR_338.8_369.2 CO8G_HUMAN 33.61179024 APLTKPLK_289.9_357.2
CRP_HUMAN 33.59900279 YSHYNER_323.5_418.2 HABP2_HUMAN 33.50888447
TSYQVYSK_488.2_787.4 C163A_HUMAN 33.11650018
IALGGLLFPASNLR_481.3_657.4 SHBG_HUMAN 33.02974341
TGISPLALIK_506.8_741.5 APOB_HUMAN 32.64471573 LYYGDDEK_501.7_726.3
CO8A_HUMAN 32.60782458 IVLSLDVPIGLLQILLEQAR_735.1_503.3 UCN2_HUMAN
32.37907686 EAQLPVIENK_570.8_329.2 PLMN_HUMAN 32.34049256
TGYYFDGISR_589.8_857.4 FBLN1_HUMAN 32.14526507
VGVISFAQK_474.8_580.3 TFR2_HUMAN 32.11753213 FQSVFTVTR_542.8_623.4
C1QC_HUMAN 32.11360444 TSDQIHFFFAK_447.6_659.4 ANT3_HUMAN
31.95867038 IAPQLSTEELVSLGEK_857.5_333.2 AFAM_HUMAN 31.81531364
EVFSKPISWEELLQ_852.9_260.2 FA40A_HUMAN 31.36698726
DEIPHNDIALLK_459.9_260.2 HABP2_HUMAN 31.1839869
NYFTSVAHPNLFIATK_608.3_319.2 IL1A_HUMAN 31.09867061
ITENDIQIALDDAK_779.9_632.3 APOB_HUMAN 30.77026845
DTYVSSFPR_357.8_272.2 TCEA1_HUMAN 30.67784731
TDAPDLPEENQAR_728.3_843.4 CO5_HUMAN 30.66251941
LFYADHPFIFLVR_546.6_647.4 SERPH_HUMAN 30.65831566
TEQAAVAR_423.2_487.3 FA12_HUMAN 30.44356842 AVGYLITGYQR_620.8_737.4
PZP_HUMAN 30.36425528 HSHESQDLR_370.2_288.2 HRG_HUMAN 30.34684703
IALGGLLFPASNLR_481.3_412.3 SHBG_HUMAN 30.34101643
IAQYYYTFK_598.8_884.4 F13B_HUMAN 30.23453833
SLPVSDSVLSGFEQR_810.9_723.3 CO8G_HUMAN 30.11396489
IIGGSDADIK_494.8_762.4 C1S_HUMAN 30.06572687 QTLSWTVTPK_580.8_545.3
PZP_HUMAN 30.04139865 HYFIAAVER_553.3_658.4 FA8_HUMAN 29.80239884
QVCADPSEEWVQK_788.4_374.2 CCL3_HUMAN 29.61435573
DLHLSDVFLK_396.2_366.2 CO6_HUMAN 29.60077507 NIQSVNVK_451.3_546.3
GROA_HUMAN 29.47619619 QTLSWTVTPK_580.8_818.4 PZP_HUMAN 29.40047934
HSHESQDLR_370.2_403.2 HRG_HUMAN 29.32242262 LLEVPEGR_456.8_356.2
C1S_HUMAN 29.14169137 LIENGYFHPVK_439.6_343.2 F13B_HUMAN
28.63056809 EDTPNSVWEPAK_686.8_630.3 C1S_HUMAN 28.61352686
AFTECCVVASQLR_770.9_673.4 CO5_HUMAN 28.57830281
VNHVTLSQPK_374.9_459.3 B2MG_HUMAN 28.27203693
VSFSSPLVAISGVALR_802.0_715.4 PAPP1_HUMAN 28.13008712
DPDQTDGLGLSYLSSHIANVER_796.4_456.2 GELS_HUMAN 28.06549895
VVGGLVALR_442.3_784.5 FA12_HUMAN 28.00684006
NEIVFPAGILQAPFYTR_968.5_357.2 ECE1_HUMAN 27.97758456
QVCADPSEEWVQK_788.4_275.2 CCL3_HUMAN 27.94276837
LQDAGVYR_461.2_680.3 PD1L1_HUMAN 27.88063261 IQTHSTTYR_369.5_540.3
F13B_HUMAN 27.68873826 TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN
27.66889639 ALALPPLGLAPLLNLWAKPQGR_770.5_256.2 SHBG_HUMAN
27.63105727 ALQDQLVLVAAK_634.9_289.2 ANGT_HUMAN 27.63097319
IEEIAAK_387.2_531.3 CO5_HUMAN 27.52427934 TAVTANLDIR_537.3_288.2
CHL1_HUMAN 27.44246841 VSEADSSNADWVTK_754.9_347.2 CFAB_HUMAN
27.43976782 ITENDIQIALDDAK_779.9_873.5 APOB_HUMAN 27.39263522
SSNNPHSPIVEEFQVPYNK_729.4_521.3 C1S_HUMAN 27.34493617
HPWIVHWDQLPQYQLNR_744.0_918.5 KS6A3_HUMAN 27.19681613
TPSAAYLWVGTGASEAEK_919.5_428.2 GELS_HUMAN 27.17319953
AFLEVNEEGSEAAASTAVVIAGR_764.4_614.4 ANT3_HUMAN 27.10487351
WGAAPYR_410.7_634.3 PGRP2_HUMAN 27.09930054
IEVNESGTVASSSTAVIVSAR_693.0_545.3 PAI1_HUMAN 27.02567296
AEAQAQYSAAVAK_654.3_908.5 ITIH4_HUMAN 26.98305259
VPLALFALNR_557.3_917.6 PEPD_HUMAN 26.96988826 TLEAQLTPR_514.8_685.4
HEP2_HUMAN 26.94672621 QALEEFQK_496.8_551.3 CO8B_HUMAN 26.67037155
WNFAYWAAHQPWSR_607.3_545.3 PRG2_HUMAN 26.62600679
IYLQPGR_423.7_570.3 ITIH2_HUMAN 26.58752589 FFQYDTWK_567.8_840.4
IGF2_HUMAN 26.39942037 NEIWYR_440.7_357.2 FA12_HUMAN 26.35177282
GGEGTGYFVDFSVR_745.9_722.4 HRG_HUMAN 26.31688167
VGEYSLYIGR_578.8_708.4 SAMP_HUMAN 26.17367498
TAHISGLPPSTDFIVYLSGLAPSIR_871.5_800.5 TENA_HUMAN 26.13688183
GVTGYFTFNLYLK_508.3_260.2 PSG5_HUMAN 26.06007032
DYWSTVK_449.7_620.3 APOC3_HUMAN 26.03765187 YENYTSSFFIR_713.8_756.4
IL12B_HUMAN 25.9096605 YGLVTYATYPK_638.3_334.2 CFAB_HUMAN
25.84440452 LFIPQITR_494.3_614.4 PSG9_HUMAN 25.78081129
YEFLNGR_449.7_606.3 PLMN_HUMAN 25.17159874 SEPRPGVLLR_375.2_454.3
FA7_HUMAN 25.16444381 NSDQEIDFK_548.3_294.2 S10A5_HUMAN 25.12266401
YEVQGEVFTKPQLWP_911.0_293.1 CRP_HUMAN 24.77595195
GVTGYFTFNLYLK_508.3_683.9 PSG5_HUMAN 24.75289081
ISLLLIESWLEPVR_834.5_371.2 CSH_HUMAN 24.72379326
ALLLGWVPTR_563.3_373.2 PAR4_HUMAN 24.68096599
VNHVTLSQPK_374.9_244.2 B2MG_HUMAN 24.53420489
SGAQATWTELPWPHEK_613.3_793.4 HEMO_HUMAN 24.25610995
AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN 24.18769142
DLPHITVDR_533.3_490.3 MMP7_HUMAN 24.02606052
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 24.00163743
AVGYLITGYQR_620.8_523.3 PZP_HUMAN 23.93958524
GFQALGDAADIR_617.3_717.4 TIMP1_HUMAN 23.69249513
YEVQGEVFTKPQLWP_911.0_392.2 CRP_HUMAN 23.67764212
SDGAKPGPR_442.7_459.2 COLI_HUMAN 23.63551614
GFQALGDAADIR_617.3_288.2 TIMP1_HUMAN 23.55832742
IAPQLSTEELVSLGEK_857.5_533.3 AFAM_HUMAN 23.38139357
DTDTGALLFIGK_625.8_217.1 PEDF_HUMAN 23.33375418
LHEAFSPVSYQHDLALLR_699.4_380.2 FA12_HUMAN 23.27455931
IYLQPGR_423.7_329.2 ITIH2_HUMAN 23.19122626
TABLE-US-00039 TABLE 38 Random Forest 32 Middle Window Variable
UniProt_ID MeanDecreaseGini SEYGAALAWEK_612.8_788.4 CO6_HUMAN
2.27812193 LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 2.080133179
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 1.952233942
ELPQSIVYK_538.8_417.7 FBLN3_HUMAN 1.518833357
VEHSDLSFSK_383.5_234.1 B2MG_HUMAN 1.482593086 VFQFLEK_455.8_811.4
CO5_HUMAN 1.448810425 VNHVTLSQPK_374.9_244.2 B2MG_HUMAN 1.389922815
YGIEEHGK_311.5_599.3 CXA1_HUMAN 1.386794676 TLAFVR_353.7_492.3
FA7_HUMAN 1.371530925 VLEPTLK_400.3_587.3 VTDB_HUMAN 1.368583173
VLEPTLK_400.3_458.3 VTDB_HUMAN 1.336029064
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 1.307024357
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 1.282930911
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 1.25362163
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 1.205539225 VEHSDLSFSK_383.5_468.2
B2MG_HUMAN 1.201047302 SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN
1.189617326 SEYGAALAWEK_612.8_845.5 CO6_HUMAN 1.120706696
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 1.107036657
VNHVTLSQPK_374.9_459.3 B2MG_HUMAN 1.083264902 IEEIAAK_387.2_660.4
CO5_HUMAN 1.043635292 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN
0.962643698 TLLPVSKPEIR_418.3_514.3 CO5_HUMAN 0.933440467
TEQAAVAR_423.2_615.4 FA12_HUMAN 0.878933553 DLHLSDVFLK_396.2_260.2
CO6_HUMAN 0.816855601 ALQDQLVLVAAK_634.9_289.2 ANGT_HUMAN
0.812620232 SLQAFVAVAAR_566.8_804.5 IL23A_HUMAN 0.792274782
QGHNSVFLIK_381.6_260.2 HEMO_HUMAN 0.770830031
ALQDQLVLVAAK_634.9_956.6 ANGT_HUMAN 0.767468246
SLDFTELDVAAEK_719.4_874.5 ANGT_HUMAN 0.745827911
TABLE-US-00040 TABLE 39 Random Forest 100 Middle Window Variable
UniProt_ID MeanDecreaseGini SEYGAALAWEK_612.8_788.4 CO6_HUMAN
1.241568411 ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.903126414
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 0.846216563
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.748261193
VFQFLEK_455.8_811.4 CO5_HUMAN 0.717545171 VEHSDLSFSK_383.5_234.1
B2MG_HUMAN 0.683219617 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN
0.671091545 LNIGYIEDLK_589.3_950.5 PAI2_HUMAN 0.652293621
VLEPTLK_400.3_587.3 VTDB_HUMAN 0.627095631 VNHVTLSQPK_374.9_244.2
B2MG_HUMAN 0.625773888 VLEPTLK_400.3_458.3 VTDB_HUMAN 0.613655529
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.576305627
TLFIFGVTK_513.3_811.5 PSG4_HUMAN 0.574056825 YGIEEHGK_311.5_599.3
CXA1_HUMAN 0.570270447 VPLALFALNR_557.3_620.4 PEPD_HUMAN
0.556087614 EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.531461012
VEHSDLSFSK_383.5_468.2 B2MG_HUMAN 0.531214597 TLAFVR_353.7_492.3
FA7_HUMAN 0.53070743 DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN
0.521633041 SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.514509661
SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 0.50489698
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.4824926
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 0.48217238
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.472286273
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 0.470892051
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 0.465839813
GEVTYTTSQVSK_650.3_750.4 EGLN_HUMAN 0.458736205
VNHVTLSQPK_374.9_459.3 B2MG_HUMAN 0.454348892 HFQNLGK_422.2_527.2
AFAM_HUMAN 0.45127405 YGIEEHGK_311.5_341.2 CXA1_HUMAN
0.430641646
TABLE-US-00041 TABLE 40 Random Forest Protein Middle Window
Variable UniProt_ID MeanDecreaseGini SEYGAALAWEK_612.8_788.4
CO6_HUMAN 2.09649626 LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN
1.27664656 VFQFLEK_455.8_811.4 CO5_HUMAN 1.243884833
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 1.231814882
VEHSDLSFSK_383.5_234.1 B2MG_HUMAN 1.188808078 ELPQSIVYK_538.8_417.7
FBLN3_HUMAN 1.185075445 LNIGYIEDLK_589.3_950.5 PAI2_HUMAN
1.122351536 VLEPTLK_400.3_458.3 VTDB_HUMAN 1.062664798
VPLALFALNR_557.3_620.4 PEPD_HUMAN 1.019466776 TLAFVR_353.7_492.3
FA7_HUMAN 0.98797064 TLFIFGVTK_513.3_811.5 PSG4_HUMAN 0.980159531
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.960286027
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.947091926
YGIEEHGK_311.5_599.3 CXA1_HUMAN 0.946937719
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.916262164
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 0.891310053
SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 0.884498494
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.869043942 HFQNLGK_422.2_527.2
AFAM_HUMAN 0.865435217 AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN
0.844842109 TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.792615068
DVLLLVHNLPQNLTGHIWYK_791.8_310.2 PSG7_HUMAN 0.763629346
GPITSAAELNDPQSILLR_632.4_826.5 EGLN_HUMAN 0.762305265
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_598.4 SHBG_HUMAN 0.706312721
SLQNASAIESILK_687.4_860.5 IL3_HUMAN 0.645503581
HYINLITR_515.3_301.1 NPY_HUMAN 0.62631682
VELAPLPSWQPVGK_760.9_342.2 ICAM1_HUMAN 0.608991877
LQVNTPLVGASLLR_741.0_925.6 BPIA1_HUMAN 0.607801279
TLEAQLTPR_514.8_814.4 HEP2_HUMAN 0.597771074 SDGAKPGPR_442.7_459.2
COLI_HUMAN 0.582773073
TABLE-US-00042 TABLE 41 Random Forest All Middle Window Variable
UniProt_ID MeanDecreaseGini SEYGAALAWEK_612.8_788.4 CO6_HUMAN
0.493373282 ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.382180772
VFQFLEK_455.8_811.4 CO5_HUMAN 0.260292083
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 0.243156718
NADYSYSVWK_616.8_769.4 CO5_HUMAN 0.242388196 VLEPTLK_400.3_458.3
VTDB_HUMAN 0.238171849 VEHSDLSFSK_383.5_234.1 B2MG_HUMAN
0.236873731 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN 0.224727161
VLEPTLK_400.3_587.3 VTDB_HUMAN 0.222105614 TLFIFGVTK_513.3_811.5
PSG4_HUMAN 0.210807574 ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN
0.208714978 LNIGYIEDLK_589.3_950.5 PAI2_HUMAN 0.208027555
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.197362212
VNHVTLSQPK_374.9_244.2 B2MG_HUMAN 0.195728091 YGIEEHGK_311.5_599.3
CXA1_HUMAN 0.189969499 HFQNLGK_422.2_527.2 AFAM_HUMAN 0.189572857
AGITIPR_364.2_486.3 IL17_HUMAN 0.188351054
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.185069517
SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 0.173688295 TLAFVR_353.7_492.3
FA7_HUMAN 0.170636045 SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.170608352
TLLIANETLR_572.3_703.4 IL5_HUMAN 0.16745571
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.161514946
LHEAFSPVSYQHDLALLR_699.4_251.2 FA12_HUMAN 0.15852146
DGSPDVTTADIGANTPDATK_973.5_844.4 PGRP2_HUMAN 0.154028378
VPLALFALNR_557.3_620.4 PEPD_HUMAN 0.153725879
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 0.150920884
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.150319671
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 0.144781622 IEEIAAK_387.2_660.4
CO5_HUMAN 0.141983196
TABLE-US-00043 TABLE 42 Random Forest 32 Middle-Late Window
Variable UniProt_ID MeanDecreaseGini VPLALFALNR_557.3_620.4
PEPD_HUMAN 4.566619475 VFQFLEK_455.8_811.4 CO5_HUMAN 3.062474666
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 3.033740627
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 2.825082394
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 2.787777983
TLAFVR_353.7_492.3 FA7_HUMAN 2.730532075
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 2.671290375
AVYEAVLR_460.8_587.4 PEPD_HUMAN 2.621357053 SEPRPGVLLR_375.2_654.4
FA7_HUMAN 2.57568964 TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 2.516708906
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 2.497348374
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 2.457401462 YGIEEHGK_311.5_599.3
CXA1_HUMAN 2.396824268 VLEPTLK_400.3_587.3 VTDB_HUMAN 2.388105564
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 2.340473883
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 2.332007976
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 2.325669514
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 2.31761671 QINSYVK_426.2_496.3
CBG_HUMAN 2.245221163 QINSYVK_426.2_610.3 CBG_HUMAN 2.212307699
TEQAAVAR_423.2_615.4 FA12_HUMAN 2.105860336 AVYEAVLR_460.8_750.4
PEPD_HUMAN 2.098321893 TEQAAVAR_423.2_487.3 FA12_HUMAN 2.062684763
DFNQFSSGEK_386.8_333.2 FETA_HUMAN 2.05160689
SLQAFVAVAAR_566.8_804.5 IL23A_HUMAN 1.989521006
SLDFTELDVAAEK_719.4_316.2 ANGT_HUMAN 1.820628782
DPTFIPAPIQAK_433.2_556.3 ANGT_HUMAN 1.763514326
DPTFIPAPIQAK_433.2_461.2 ANGT_HUMAN 1.760870392 VLEPTLK_400.3_458.3
VTDB_HUMAN 1.723389354 YENYTSSFFIR_713.8_756.4 IL12B_HUMAN
1.63355187
TABLE-US-00044 TABLE 43 Random Forest 100 Middle-Late Window
Variable UniProt_ID MeanDecreaseGini VPLALFALNR_557.3_620.4
PEPD_HUMAN 1.995805024 VFQFLEK_455.8_811.4 CO5_HUMAN 1.235926416
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 1.187464899
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 1.166642578
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 1.146077071
TLAFVR_353.7_492.3 FA7_HUMAN 1.143038275
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 1.130656591
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 1.098305298
ELPQSIVYK_538.8_417.7 FBLN3_HUMAN 1.096715712
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 1.086171713
YGIEEHGK_311.5_341.2 CXA1_HUMAN 1.071880823
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 1.062278869
TQILEWAAER_608.8_761.4 EGLN_HUMAN 1.059019017 AVYEAVLR_460.8_587.4
PEPD_HUMAN 1.057920661 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 1.038388955
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 1.028275728
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 1.026032369
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 1.015065282 YGIEEHGK_311.5_599.3
CXA1_HUMAN 0.98667651 VLEPTLK_400.3_587.3 VTDB_HUMAN 0.970330675
DVLLLVHNLPQNLTGHIWYK_791.8_883.0 PSG7_HUMAN 0.934747674
TAHISGLPPSTDFIVYLSGLAPSIR_871.5_472.3 TENA_HUMAN 0.889111923
TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.887605636
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 0.884305889
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.880889836
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.863585472
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.849232356
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.843334824
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.842319271
TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN 0.828959173
TABLE-US-00045 TABLE 44 Random Forest Protein Middle-Late Window
Variable UniProt_ID MeanDecreaseGini VPLALFALNR_557.3_620.4
PEPD_HUMAN 3.202123047 ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN
2.100447309 VFQFLEK_455.8_811.4 CO5_HUMAN 2.096157529
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 2.052960939
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 2.046139797
TQILEWAAER_608.8_761.4 EGLN_HUMAN 1.99287941 ELPQSIVYK_538.8_417.7
FBLN3_HUMAN 1.920894959 TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN
1.917665697 SEPRPGVLLR_375.2_654.4 FA7_HUMAN 1.883557705
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 1.870232155
EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 1.869000136
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 1.825457092 VLEPTLK_400.3_587.3
VTDB_HUMAN 1.695327774 TEQAAVAR_423.2_615.4 FA12_HUMAN 1.685013152
LLAPSDSPEWLSFDVTGVVR_730.1_430.3 TGFB1_HUMAN 1.684068039
TLNAYDHR_330.5_312.2 PAR3_HUMAN 1.673758239
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 1.648896853
DVLLLVHNLPQNLTGHIWYK_791.8_883.0 PSG7_HUMAN 1.648146088
AEIEYLEK_497.8_552.3 LYAM1_HUMAN 1.645833005 TYLHTYESEI_628.3_515.3
ENPP2_HUMAN 1.639121965 AGLLRPDYALLGHR_518.0_595.4 PGRP2_HUMAN
1.610227875 YGIEEHGK_311.5_599.3 CXA1_HUMAN 1.606978339
QINSYVK_426.2_496.3 CBG_HUMAN 1.554905578 LTTVDIVTLR_565.8_815.5
IL2RB_HUMAN 1.484081016 AALAAFNAQNNGSNFQLEEISR_789.1_746.4
FETUA_HUMAN 1.43173022 AEVIWTSSDHQVLSGK_586.3_300.2 PD1L1_HUMAN
1.394857397 ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN 1.393464547
DFNQFSSGEK_386.8_333.2 FETA_HUMAN 1.374296237 TSYQVYSK_488.2_787.4
C163A_HUMAN 1.36141387 TLEAQLTPR_514.8_685.4 HEP2_HUMAN
1.311118611
TABLE-US-00046 TABLE 45 Random Forest All Middle-Late Window
Variable UniProt_ID MeanDecreaseGini VPLALFALNR_557.3_620.4
PEPD_HUMAN 0.685165163 VFQFLEK_455.8_811.4 CO5_HUMAN 0.426827804
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.409942379
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.406589512
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.402152062
AQPVQVAEGSEPDGFWEALGGK_758.0_574.3 GELS_HUMAN 0.374861014
ANLINNIFELAGLGK_793.9_299.2 LCAP_HUMAN 0.367089422
TQILEWAAER_608.8_761.4 EGLN_HUMAN 0.353757524 AVYEAVLR_460.8_587.4
PEPD_HUMAN 0.350518668 TLAFVR_353.7_492.3 FA7_HUMAN 0.344669505
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.338752336 LIEIANHVDK_384.6_683.4
ADA12_HUMAN 0.321850027 ELPQSIVYK_538.8_417.7 FBLN3_HUMAN
0.301819017 EVFSKPISWEELLQ_852.9_376.2 FA40A_HUMAN 0.299561811
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 0.298253589 VLEPTLK_400.3_587.3
VTDB_HUMAN 0.296206088 YGIEEHGK_311.5_599.3 CXA1_HUMAN 0.295621408
DVLLLVHNLPQNLTGHIWYK_791.8_883.0 PSG7_HUMAN 0.292937475
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.275902848
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.275664578
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.27120436
AVDIPGLEAATPYR_736.9_399.2 TENA_HUMAN 0.266568271
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.262537889
TLNAYDHR_330.5_312.2 PAR3_HUMAN 0.259901193 IYLQPGR_423.7_329.2
ITIH2_HUMAN 0.259086112 AEVIWTSSDHQVLSGK_586.3_300.2 PD1L1_HUMAN
0.25722354 VPSHAVVAR_312.5_515.3 TRFL_HUMAN 0.256151812
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.251704855
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 0.249400642
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.245930393
TABLE-US-00047 TABLE 46 Random Forest 32 Late Window Variable
UniProt_ID MeanDecreaseGini AVYEAVLR_460.8_587.4 PEPD_HUMAN
1.889521223 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 1.75233545
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 1.676813493
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 1.600684153
AVYEAVLR_460.8_750.4 PEPD_HUMAN 1.462889662 LIEIANHVDK_384.6_683.4
ADA12_HUMAN 1.364115361 VPLALFALNR_557.3_620.4 PEPD_HUMAN
1.324317148 QINSYVK_426.2_610.3 CBG_HUMAN 1.305932064
ITQDAQLK_458.8_702.4 CBG_HUMAN 1.263533228
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 1.245153376
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 1.236529173 QINSYVK_426.2_496.3
CBG_HUMAN 1.221866266 YSHYNER_323.5_418.2 HABP2_HUMAN 1.169575572
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 1.126684146 VGVISFAQK_474.8_580.3
TFR2_HUMAN 1.075283855 VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN
1.07279097 SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN 1.05759256
DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 1.028933332
ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN 1.014443799
ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN 1.010573267 ILDGGNK_358.7_603.3
CXCL5_HUMAN 0.992175141 TSYQVYSK_488.2_787.4 C163A_HUMAN 0.95649585
YENYTSSFFIR_713.8_756.4 IL12B_HUMAN 0.955085198
SETEIHQGFQHLHQLFAK_717.4_447.2 CBG_HUMAN 0.944726739
TLPFSR_360.7_506.3 LYAM1_HUMAN 0.944426109 VLSSIEQK_452.3_691.4
1433S_HUMAN 0.933902495 AEIEYLEK_497.8_389.2 LYAM1_HUMAN
0.891235263 GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN 0.87187037
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 0.869821307
SGVDLADSNQK_567.3_591.3 VGFR3_HUMAN 0.839946466
TABLE-US-00048 TABLE 47 Random Forest 100 Late Window Variable
UniProt_ID MeanDecreaseGini AVYEAVLR_460.8_587.4 PEPD_HUMAN
0.971695767 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 0.920098693
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.786924487
AVYEAVLR_460.8_750.4 PEPD_HUMAN 0.772867983
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 0.744138513
AYSDLSR_406.2_375.2 SAMP_HUMAN 0.736078079 VPLALFALNR_557.3_620.4
PEPD_HUMAN 0.681784822 QINSYVK_426.2_610.3 CBG_HUMAN 0.585819307
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 0.577161158
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.573055613
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.569156128
ITQDAQLK_458.8_702.4 CBG_HUMAN 0.551017844 LIEIANHVDK_384.6_683.4
ADA12_HUMAN 0.539330047 YYGYTGAFR_549.3_450.3 TRFL_HUMAN
0.527652175 VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN 0.484155289
FQLPGQK_409.2_429.2 PSG1_HUMAN 0.480394031
AVDIPGLEAATPYR_736.9_286.1 TENA_HUMAN 0.475252565
QINSYVK_426.2_496.3 CBG_HUMAN 0.4728541 YISPDQLADLYK_713.4_277.2
ENOA_HUMAN 0.470079977 TLPFSR_360.7_506.3 LYAM1_HUMAN 0.46881451
SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN 0.4658941
ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN 0.463604174 YSHYNER_323.5_418.2
HABP2_HUMAN 0.453076307 VGVISFAQK_474.8_580.3 TFR2_HUMAN
0.437768219 LQDAGVYR_461.2_680.3 PD1L1_HUMAN 0.428524689
AEIEYLEK_497.8_389.2 LYAM1_HUMAN 0.42041448 TSYQVYSK_488.2_787.4
C163A_HUMAN 0.419411932 SVVLIPLGAVDDGEHSQNEK_703.0_798.4
CNDP1_HUMAN 0.415325735 ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN
0.407951733 ILDGGNK_358.7_603.3 CXCL5_HUMAN 0.401059572
TABLE-US-00049 TABLE 48 Random Forest Protein Late Window Variable
UniProt_ID MeanDecreaseGini AVYEAVLR_460.8_587.4 PEPD_HUMAN
1.836010146 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 1.739802548
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 1.455337749
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 1.395043941
AYSDLSR_406.2_375.2 SAMP_HUMAN 1.177349958 LIEIANHVDK_384.6_683.4
ADA12_HUMAN 1.14243936 QINSYVK_426.2_496.3 CBG_HUMAN 1.05284482
ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN 0.971678206
YISPDQLADLYK_713.4_277.2 ENOA_HUMAN 0.902293734
AVDIPGLEAATPYR_736.9_286.1 TENA_HUMAN 0.893163413
SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN 0.856551531
ILDGGNK_358.7_603.3 CXCL5_HUMAN 0.841485153 VGVISFAQK_474.8_580.3
TFR2_HUMAN 0.835256078 YYGYTGAFR_549.3_450.3 TRFL_HUMAN 0.831195917
YSHYNER_323.5_418.2 HABP2_HUMAN 0.814479968 FQLPGQK_409.2_276.1
PSG1_HUMAN 0.77635168 YENYTSSFFIR_713.8_756.4 IL12B_HUMAN
0.761241391 TEQAAVAR_423.2_615.4 FA12_HUMAN 0.73195592
SGVDLADSNQK_567.3_662.3 VGFR3_HUMAN 0.72504131 VLSSIEQK_452.3_691.4
1433S_HUMAN 0.713380314 GTYLYNDCPGPGQDTDCR_697.0_666.3 TNR1A_HUMAN
0.704248586 TSYQVYSK_488.2_787.4 C163A_HUMAN 0.69026345
TLEAQLTPR_514.8_685.4 HEP2_HUMAN 0.654641588
AEVIWTSSDHQVLSGK_586.3_300.2 PD1L1_HUMAN 0.634751081
TAVTANLDIR_537.3_288.2 CHL1_HUMAN 0.619871203
ITENDIQIALDDAK_779.9_632.3 APOB_HUMAN 0.606313398
TASDFITK_441.7_781.4 GELS_HUMAN 0.593535076 SPQAFYR_434.7_556.3
REL3_HUMAN 0.592004045 NHYTESISVAK_624.8_415.2 NEUR1_HUMAN
0.588383911 LTTVDIVTLR_565.8_815.5 IL2RB_HUMAN 0.587343951
TABLE-US-00050 TABLE 49 Random Forest All Late Window Variable
UniProt_ID MeanDecreaseGini AVYEAVLR_460.8_587.4 PEPD_HUMAN
0.437300283 AEIEYLEK_497.8_552.3 LYAM1_HUMAN 0.371624293
AALAAFNAQNNGSNFQLEEISR_789.1_746.4 FETUA_HUMAN 0.304039734
TGVAVNKPAEFTVDAK_549.6_258.1 FLNA_HUMAN 0.280588526
AVYEAVLR_460.8_750.4 PEPD_HUMAN 0.266788699 AYSDLSR_406.2_375.2
SAMP_HUMAN 0.247412666 VPLALFALNR_557.3_620.4 PEPD_HUMAN
0.229955358 LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.218186524
ITQDAQLK_458.8_702.4 CBG_HUMAN 0.217646659
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.213840705
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.212794469
LIEIANHVDK_384.6_498.3 ADA12_HUMAN 0.208620264 QINSYVK_426.2_610.3
CBG_HUMAN 0.202054546 QINSYVK_426.2_496.3 CBG_HUMAN 0.197235139
FQLPGQK_409.2_429.2 PSG1_HUMAN 0.188311102
VFQYIDLHQDEFVQTLK_708.4_375.2 CNDP1_HUMAN 0.180534913
ALEQDLPVNIK_620.4_798.5 CNDP1_HUMAN 0.178464358
YYGYTGAFR_549.3_450.3 TRFL_HUMAN 0.176050092
ALFLDALGPPAVTR_720.9_640.4 INHA_HUMAN 0.171492975
FQLPGQK_409.2_276.1 PSG1_HUMAN 0.167576198
SETEIHQGFQHLHQLFAK_717.4_447.2 CBG_HUMAN 0.162231844
ALEQDLPVNIK_620.4_570.4 CNDP1_HUMAN 0.162165399
VPSHAVVAR_312.5_515.3 TRFL_HUMAN 0.156742065
AVDIPGLEAATPYR_736.9_286.1 TENA_HUMAN 0.153681405
FTFTLHLETPKPSISSSNLNPR_829.4_874.4 PSG1_HUMAN 0.152042057
VGVISFAQK_474.8_580.3 TFR2_HUMAN 0.149034355 TLPFSR_360.7_506.3
LYAM1_HUMAN 0.143223501 SLDFTELDVAAEK_719.4_874.5 ANGT_HUMAN
0.141216186 SPEAEDPLGVER_649.8_314.1 Z512B_HUMAN 0.139843479
YGIEEHGK_311.5_341.2 CXA1_HUMAN 0.135236953
TABLE-US-00051 TABLE 50 Selected Transitions for Early Window
Transition Parent Protein LIQDAVTGLTVNGQITGDK_972.0_798.4
ITIH3_HUMAN VQTAHFK_277.5_431.2 CO8A_HUMAN FLNWIK_410.7_560.3
HABP2_HUMAN ITGFLKPGK_320.9_429.3 LBP_HUMAN
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN TYLHTYESEI_628.3_908.4
ENPP2_HUMAN LIENGYFHPVK_439.6_627.4 F13B_HUMAN AVLHIGEK_289.5_292.2
THBG_HUMAN QALEEFQK_496.8_680.3 CO8B_HUMAN
TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN
TASDFITK_441.7_781.4 GELS_HUMAN LPNNVLQEK_527.8_844.5 AFAM_HUMAN
AHYDLR_387.7_288.2 FETUA_HUMAN ITLPDFTGDLR_624.3_288.2 LBP_HUMAN
IEGNLIFDPNNYLPK_874.0_414.2 APOB_HUMAN ITGFLKPGK_320.9_301.2
LBP_HUMAN FSVVYAK_407.2_381.2 FETUA_HUMAN ITGFLKPGK_320.9_429.3
LBP_HUMAN VFQFLEK_455.8_811.4 CO5_HUMAN
LIQDAVTGLTVNGQITGDK_972.0_798.4 ITIH3_HUMAN DADPDTFFAK_563.8_825.4
AFAM_HUMAN
TABLE-US-00052 TABLE 51 Selected Proteins for Early Window Protein
complement component C6 precursor CO6_HUMAN inter-alpha-trypsin
inhibitor heavy chain H3 ITIH3_HUMAN preproprotein Coagulation
factor XIII B chain F13B_HUMAN Ectonucleotide
pyrophosphatase/phosphodiesterase ENPP2_HUMAN family member 2
Complement component C8 beta chain CO8B_HUMAN thyroxine-binding
globulin precursor THBG_HUMAN Hyaluronan-binding protein 2
HABP2_HUMAN lipopolysaccharide-binding protein LBP_HUMAN Complement
factor B CFAB_HUMAN Gelsolin GELS_HUMAN afamin precursor AFAM_HUMAN
apolipoprotein B-100 precursor APOB_HUMAN complement component C5
CO5_HUMAN Alpha-2-HS-glycoprotein FETUA_HUMAN complement component
C8 gamma chain CO8G_HUMAN
TABLE-US-00053 TABLE 52 Selected Transitions for Middle-Late Window
Transition Patent Protein VPLALFALNR_557.3_620.4 PEPD_HUMAN
VFQFLEK_455.8_811.4 CO5_HUMAN AQPVQVAEGSEPDGFWEALGGK_758.0_574.3
GELS_HUMAN LIEIANHVDK_384.6_498.3 ADA12_HUMAN TLAFVR_353.7_492.3
FA7_HUMAN ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN
AVYEAVLR_460.8_587.4 PEPD_HUMAN SEPRPGVLLR_375.2_654.4 FA7_HUMAN
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN ALNHLPLEYNSALYSR_621.0_538.3
CO6_HUMAN
TABLE-US-00054 TABLE 53 Selected Proteins for Middle-Late Window
Protein Xaa-Pro dipeptidase PEPD_HUMAN Leucyl-cystinyl
aminopeptidase LCAP_HUMAN complement component C5 CO5_HUMAN
Gelsolin GELS_HUMAN complement component C6 precursor CO6_HUMAN
Endoglin precursor EGLN_HUMAN EGF-containing fibulin-like
extracellular matrix FBLN3_HUMAN protein 1 coagulation factor VII
isoform a FA7_HUMAN Disintegrin and metalloproteinase domain-
ADA12_HUMAN containing protein 12 vitamin D-binding protein isoform
1 precursor VTDB_HUMAN coagulation factor XII precursor FA12_HUMAN
Corticosteroid-binding globulin CBG_HUMAN
Example 6
Study V to Further Refine Preterm Birth Biomarkers
[0186] A additional hypothesis-dependent discovery study was
performed with a further refined scheduled MRM assay. Less robust
transitions were again removed to improve analytical performance
and make room for the inclusion of stable-isotope labeled standards
(SIS) corresponding to 79 analytes of interest identified in
previous studies. SIS peptides have identical amino acid sequence,
chromatographic and MS fragmentation behaviour as their endogenous
peptide counterparts, but differ in mass. Therefore they can be
used to reduce LC-MS analytical variability and confirm analyte
identity. Samples included approximately 60 spontaneous PTB cases
(delivery at less than 37 weeks, 0 days), and 180 term controls
(delivery at greater than or equal to 37 weeks, 0 days). Each case
was designated a "matched" control to within one day of blood draw
and two "random" controls matched to the same 3 week blood draw
window (17-19, 20-22 or 23-25 weeks gestation). For the purposes of
analysis these three blood draw windows were combined. Samples were
processed essentially as described previously, except that in this
study, tryptic digests were reconstituted in a solution containing
SIS standards. Raw analyte peak areas were Box-Cox transformed,
corrected for run order and batch effects by regression and used
for univariate and multivariate statistical analyses. Univariate
analysis included determination of p-values for adjusted peak areas
for all analytes from t-tests considering cases vs controls defined
as either deliveries at >37 weeks (Table 54) or deliveries at
>40 weeks (Table 55). Univariate analysis also included the
determination of p-values for a linear model that evaluates the
dependence of each analyte's adjusted peak area on the time to
birth (gestational age at birth minus the gestational age at blood
draw) (Table 56) and the gestational age at birth (Table 57).
Additionally raw peak area ratios were calculated for endogenous
analytes and their corresponding SIS counterparts, Box-Cox
transformed and then used for univariate and multivariate
statistical analyses. The above univariate analysis was repeated
for analyte/SIS peak area ratio values, summarized in Tables 58-61,
respectively.
[0187] Multivariate random forest regression models were built
using analyte values and clinical variables (e.g. Maternal age,
(MAGE), Body mass index, (BMI)) to predict Gestational Age at Birth
(GAB). The accuracy of the random forest was evaluated with respect
to correlation of the predicted and actual GAB, and with respect to
the mean absolute deviation (MAD) of the predicted from actual GAB.
The accuracy was further evaluated by determining the area under
the receiver operating characteristic curve (AUC) when using the
predicted GAB as a quantitative variable to classify subjects as
full term or pre-term. Random Forest Importance Values were fit to
an Empirical Cumulative Disribution Function and probabilities (P)
were calculated. We report the analytes by importance ranking
(P>0.7) in the random forest models, using adjusted analyte peak
area values (Table 62) and analyte/SIS peak area ratio values
(Table 63).
[0188] The probability of pre-term birth, p(PTB), may be estimated
using the predicted gestational age at birth (GAB) as follows. The
estimate will be based on women enrolled in the Sera PAPR clinical
trial, which provided the subjects used to develop the PTB
prediction methods.
[0189] Among women with a predicted GAB of j days plus or minus k
days, p(PTB) was estimated as the proportion of women in the PAPR
clinical trial with a predicted GAB of j days plus or minus k days
who actually deliver before 37 weeks gestational age.
[0190] More generally, for women with a predicted GAB of j days
plus or minus k days, the probability that the actual gestational
age at birth will be less than a specified gestational age,
p(actual GAB <specified GAB), was estimated as the proportion of
women in the PAPR clinical trial with a predicted GAB of j days
plus or minus k days who actually deliver before the specified
gestational age. FIG. 1 depicts a scatterplot of actual gestational
age at birth versus predicted gestational age from random forest
regression model. FIG. 2 shows the distribution of predicted
gestational age from random forest regression model versus actual
gestational age at birth (GAB), where actual GAB was given in
categories of (i) less than 37 weeks, (ii) 37 to 39 weeks, and
(iii) 40 weeks or greater.
TABLE-US-00055 TABLE 54 Univariate p-values for Adjusted Peak Areas
(<37 vs >37 weeks) Transition Protein pvalue
SPELQAEAK_486.8_659.4 APOA2_HUMAN 0.00246566
ALALPPLGLAPLLNLWAKPQGR_770.5_457.3 SHBG_HUMAN 0.002623332
ALALPPLGLAPLLNLWAKPQGR_770.5_256.2 SHBG_HUMAN 0.002822593
SPELQAEAK_486.8_788.4 APOA2_HUMAN 0.003183869
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_768.5 SHBG_HUMAN 0.004936049
VVLSSGSGPGLDLPLVLGLPLQLK_791.5_598.4 SHBG_HUMAN 0.005598977
DYWSTVK_449.7_347.2 APOC3_HUMAN 0.005680405 DYWSTVK_449.7_620.3
APOC3_HUMAN 0.006288693 WGAAPYR_410.7_634.3 PGRP2_HUMAN 0.006505238
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.007626246
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 0.008149335
LSIPQITTK_500.8_687.4 PSG5_HUMAN 0.009943955
GWVTDGFSSLK_598.8_854.4 APOC3_HUMAN 0.010175055
IALGGLLFPASNLR_481.3_657.4 SHBG_HUMAN 0.010784167
AKPALEDLR_506.8_813.5 APOA1_HUMAN 0.011331968 WGAAPYR_410.7_577.3
PGRP2_HUMAN 0.011761088 VPLALFALNR_557.3_620.4 PEPD_HUMAN
0.014050395 FSLVSGWGQLLDR_493.3_447.3 FA7_HUMAN 0.014271151
LSIPQITTK_500.8_800.5 PSG5_HUMAN 0.014339942 TLAFVR_353.7_274.2
FA7_HUMAN 0.014459876 DVLLLVHNLPQNLPGYFWYK_810.4_960.5 PSG9_HUMAN
0.016720007 FSVVYAK_407.2_381.2 FETUA_HUMAN 0.016792786
DVLLLVHNLPQNLPGYFWYK_810.4_215.1 PSG9_HUMAN 0.017335929
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.018147773
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.019056484
WNFAYWAAHQPWSR_607.3_545.3 PRG2_HUMAN 0.019190043
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.020218682
AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN 0.020226218
GWVTDGFSSLK_598.8_953.5 APOC3_HUMAN 0.023192703
IALGGLLFPASNLR_481.3_412.3 SHBG_HUMAN 0.023916911
WNFAYWAAHQPWSR_607.3_673.3 PRG2_HUMAN 0.026026975
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.027731407
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.031865281
DADPDTFFAK_563.8_302.1 AFAM_HUMAN 0.0335897 LFIPQITR_494.3_614.4
PSG9_HUMAN 0.034140767 DVLLLVHNLPQNLPGYFWYK_810.4_328.2 PSG9_HUMAN
0.034653304 TLAFVR_353.7_492.3 FA7_HUMAN 0.036441189
AVLHIGEK_289.5_292.2 THBG_HUMAN 0.038539433 IHPSYTNYR_384.2_452.2
PSG2_HUMAN 0.039733019 AGLLRPDYALLGHR_518.0_369.2 PGRP2_HUMAN
0.040916226 ILILPSVTR_506.3_559.3 PSGx_HUMAN 0.042460036
YYLQGAK_421.7_516.3 ITIH4_HUMAN 0.044511962
TPSAAYLWVGTGASEAEK_919.5_849.4 GELS_HUMAN 0.046362381
AGLLRPDYALLGHR_518.0_595.4 PGRP2_HUMAN 0.046572355
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 0.04754503
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 0.048642964
VNFTEIQK_489.8_765.4 FETA_HUMAN 0.04871392 LFIPQITR_494.3_727.4
PSG9_HUMAN 0.049288923 DISEVVTPR_508.3_787.4 CFAB_HUMAN 0.049458374
SEPRPGVLLR_375.2_454.3 FA7_HUMAN 0.049567047
TABLE-US-00056 TABLE 55 Univariate p-values for Adjusted Peak Areas
(<37 vs >40 weeks) Transition Protein pvalue
SPELQAEAK_486.8_659.4 APOA2_HUMAN 0.001457796 DYWSTVK_449.7_347.2
APOC3_HUMAN 0.001619622 DYWSTVK_449.7_620.3 APOC3_HUMAN 0.002068704
DALSSVQESQVAQQAR_573.0_502.3 APOC3_HUMAN 0.00250563
GWVTDGFSSLK_598.8_854.4 APOC3_HUMAN 0.002543943
SPELQAEAK_486.8_788.4 APOA2_HUMAN 0.003108814
SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.004035832
DALSSVQESQVAQQAR_573.0_672.4 APOC3_HUMAN 0.00434652
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.005306924
GWVTDGFSSLK_598.8_953.5 APOC3_HUMAN 0.005685534
ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.005770384
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.005798991
ENPAVIDFELAPIVDLVR_670.7_601.4 CO6_HUMAN 0.006248095
ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN 0.006735817
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 0.007351774
AGLLRPDYALLGHR_518.0_369.2 PGRP2_HUMAN 0.009541521
AKPALEDLR_506.8_813.5 APOA1_HUMAN 0.009780371
SEYGAALAWEK_612.8_845.5 CO6_HUMAN 0.010085363
FSLVSGWGQLLDR_493.3_447.3 FA7_HUMAN 0.010401836 WGAAPYR_410.7_634.3
PGRP2_HUMAN 0.011233623 ENPAVIDFELAPIVDLVR_670.7_811.5 CO6_HUMAN
0.012029564 DVLLLVHNLPQNLPGYFWYK_810.4_215.1 PSG9_HUMAN 0.014808277
LFIPQITR_494.3_614.4 PSG9_HUMAN 0.015879755 WGAAPYR_410.7_577.3
PGRP2_HUMAN 0.016562435 AGLLRPDYALLGHR_518.0_595.4 PGRP2_HUMAN
0.016793521 TLAFVR_353.7_492.3 FA7_HUMAN 0.016919708
FSLVSGWGQLLDR_493.3_403.2 FA7_HUMAN 0.016937583
WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN 0.019050115
GYVIIKPLVWV_643.9_304.2 SAMP_HUMAN 0.019675317
DVLLLVHNLPQNLPGYFWYK_810.4_960.5 PSG9_HUMAN 0.020387647
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.020458335
DVLLLVHNLPQNLPGYFWYK_810.4_328.2 PSG9_HUMAN 0.021488084
WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 0.021709354
LDFHFSSDR_375.2_448.2 INHBC_HUMAN 0.022403383 LFIPQITR_494.3_727.4
PSG9_HUMAN 0.025561103 TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3
ENPP2_HUMAN 0.029344366 LSIPQITTK_500.8_800.5 PSG5_HUMAN
0.031361776 ALVLELAK_428.8_672.4 INHBE_HUMAN 0.031690737
SEPRPGVLLR_375.2_454.3 FA7_HUMAN 0.033067953 LSIPQITTK_500.8_687.4
PSG5_HUMAN 0.033972449 LDFHFSSDR_375.2_611.3 INHBC_HUMAN
0.034500249 LDFHFSSDR_375.2_464.2 INHBC_HUMAN 0.035166664
GAVHVVVAETDYQSFAVLYLER_822.8_580.3 CO8G_HUMAN 0.037334975
HELTDEELQSLFTNFANVVDK_817.1_854.4 AFAM_HUMAN 0.039258528
AYSDLSR_406.2_375.2 SAMP_HUMAN 0.04036485 YYLQGAK_421.7_516.3
ITIH4_HUMAN 0.042204165 ILPSVPK_377.2_264.2 PGH1_HUMAN 0.042397885
ELLESYIDGR_597.8_710.4 THRB_HUMAN 0.043053589
ALALPPLGLAPLLNLWAKPQGR_770.5_256.2 SHBG_HUMAN 0.045692283
VGEYSLYIGR_578.8_871.5 SAMP_HUMAN 0.04765767
ANDQYLTAAALHNLDEAVK_686.4_317.2 IL1A_HUMAN 0.048928376
YYGYTGAFR_549.3_551.3 TRFL_HUMAN 0.049568351
TABLE-US-00057 TABLE 56 Univariate p-values for Adjusted Peak Areas
in Time to Birth Linear Model Protein pvalue ADA12_HUMAN
0.003412707 ENPP2_HUMAN 0.003767393 ADA12_HUMAN 0.004194234
ENPP2_HUMAN 0.004298493 ADA12_HUMAN 0.004627197 ADA12_HUMAN
0.004918852 ENPP2_HUMAN 0.005792374 CO6_HUMAN 0.005858282
ENPP2_HUMAN 0.007123606 CO6_HUMAN 0.007162317 ENPP2_HUMAN
0.008228726 ENPP2_HUMAN 0.009168492 PSG9_HUMAN 0.011531192
PSG9_HUMAN 0.019389627 PSG9_HUMAN 0.023680865 INHBE_HUMAN
0.02581564 B2MG_HUMAN 0.026544689 LBP_HUMAN 0.031068274 PSG9_HUMAN
0.031091843 APOA2_HUMAN 0.033130498 INHBC_HUMAN 0.03395215
CBG_HUMAN 0.034710348 PSGx_HUMAN 0.035719227 CBG_HUMAN 0.036331871
CSH_HUMAN 0.039896611 CSH_HUMAN 0.04244001 SAMP_HUMAN 0.047112128
LBP_HUMAN 0.048141371 LBP_HUMAN 0.048433174 CO6_HUMAN 0.04850949
PSGx_HUMAN 0.049640167
TABLE-US-00058 TABLE 57 Univariate p-values for Adjusted Peak Areas
in Gestation Age at Birth Linear Model Transition Protein pvalue
ENPAVIDFELAPIVDLVR_670.7_811.5 CO6_HUMAN 0.000117239
ENPAVIDFELAPIVDLVR_670.7_601.4 CO6_HUMAN 0.000130113
TYLHTYESEI_628.3_908.4 ENPP2_HUMAN 0.000160472
TYLHTYESEI_628.3_515.3 ENPP2_HUMAN 0.000175167
TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 ENPP2_HUMAN 0.000219886
TEFLSNYLTNVDDITLVPGTLGR_846.8_699.4 ENPP2_HUMAN 0.000328416
WWGGQPLWITATK_772.4_373.2 ENPP2_HUMAN 0.000354644
WWGGQPLWITATK_772.4_929.5 ENPP2_HUMAN 0.000390821
SEYGAALAWEK_612.8_788.4 CO6_HUMAN 0.000511882 LDFHFSSDR_375.2_448.2
INHBC_HUMAN 0.000600637 ALVLELAK_428.8_672.4 INHBE_HUMAN
0.000732445 GLQYAAQEGLLALQSELLR_1037.1_929.5 LBP_HUMAN 0.000743924
DVLLLVHNLPQNLPGYFWYK_810.4_960.5 PSG9_HUMAN 0.000759173
FGFGGSTDSGPIR_649.3_745.4 ADA12_HUMAN 0.001224347
DVLLLVHNLPQNLPGYFWYK_810.4_328.2 PSG9_HUMAN 0.001241329
GYVIIKPLVWV_643.9_304.2 SAMP_HUMAN 0.001853785
SPELQAEAK_486.8_659.4 APOA2_HUMAN 0.001856303
GLQYAAQEGLLALQSELLR_1037.1_858.5 LBP_HUMAN 0.001978165
LDFHFSSDR_375.2_611.3 INHBC_HUMAN 0.002098948
LIEIANHVDK_384.6_683.4 ADA12_HUMAN 0.002212096 SFRPFVPR_335.9_272.2
LBP_HUMAN 0.002545286 SFRPFVPR_335.9_635.3 LBP_HUMAN 0.002620268
WSAGLTSSQVDLYIPK_883.0_515.3 CBG_HUMAN 0.002787272
DLHLSDVFLK_396.2_260.2 CO6_HUMAN 0.002954612 LIEIANHVDK_384.6_498.3
ADA12_HUMAN 0.002955081 DVLLLVHNLPQNLPGYFWYK_810.4_215.1 PSG9_HUMAN
0.003541011 LFIPQITR_494.3_614.4 PSG9_HUMAN 0.003750666
FGFGGSTDSGPIR_649.3_946.5 ADA12_HUMAN 0.003773696
YYLQGAK_421.7_516.3 ITIH4_HUMAN 0.004064026 SEYGAALAWEK_612.8_845.5
CO6_HUMAN 0.004208136 AITPPHPASQANIIFDITEGNLR_825.8_459.3
FBLN1_HUMAN 0.004709104 LDFHFSSDR_375.2_464.2 INHBC_HUMAN
0.005355741 HELTDEELQSLFTNFANVVDK_817.1_854.4 AFAM_HUMAN
0.005370567 ALNHLPLEYNSALYSR_621.0_696.4 CO6_HUMAN 0.005705922
ITQDAQLK_458.8_702.4 CBG_HUMAN 0.006762484 ITLPDFTGDLR_624.3_920.5
LBP_HUMAN 0.006993268 SILFLGK_389.2_577.4 THBG_HUMAN 0.007134146
WSAGLTSSQVDLYIPK_883.0_357.2 CBG_HUMAN 0.007670388
GVTSVSQIFHSPDLAIR_609.7_472.3 IC1_HUMAN 0.007742729
VGEYSLYIGR_578.8_871.5 SAMP_HUMAN 0.007778691
ITLPDFTGDLR_624.3_288.2 LBP_HUMAN 0.008179918 YYLQGAK_421.7_327.1
ITIH4_HUMAN 0.008404686 ALNHLPLEYNSALYSR_621.0_538.3 CO6_HUMAN
0.008601162 DYWSTVK_449.7_620.3 APOC3_HUMAN 0.008626786
TVQAVLTVPK_528.3_855.5 PEDF_HUMAN 0.008907523 ITGFLKPGK_320.9_301.2
LBP_HUMAN 0.009155417 LFIPQITR_494.3_727.4 PSG9_HUMAN 0.009571006
SPELQAEAK_486.8_788.4 APOA2_HUMAN 0.009776508 DYWSTVK_449.7_347.2
APOC3_HUMAN 0.00998356 ITGFLKPGK_320.9_429.3 LBP_HUMAN 0.010050264
FLNWIK_410.7_560.3 HABP2_HUMAN 0.010372454 DLHLSDVFLK_396.2_366.2
CO6_HUMAN 0.010806378 GVTSVSQIFHSPDLAIR_609.7_908.5 IC1_HUMAN
0.011035991 VEHSDLSFSK_383.5_468.2 B2MG_HUMAN 0.011113172
LLDSLPSDTR_558.8_276.2 IC1_HUMAN 0.011589013 LLDSLPSDTR_558.8_890.4
IC1_HUMAN 0.011629438 QALEEFQK_496.8_551.3 CO8B_HUMAN 0.011693839
LLDSLPSDTR_558.8_575.3 IC1_HUMAN 0.012159314 IIGGSDADIK_494.8_762.4
C1S_HUMAN 0.013080243 AFIQLWAFDAVK_704.9_650.4 AMBP_HUMAN
0.013462234 GFQALGDAADIR_617.3_717.4 TIMP1_HUMAN 0.014370997
LPNNVLQEK_527.8_730.4 AFAM_HUMAN 0.014424891
DTDTGALLFIGK_625.8_217.1 PEDF_HUMAN 0.014967952 VQTAHFK_277.5_502.3
CO8A_HUMAN 0.01524844 ILILPSVTR_506.3_559.3 PSGx_HUMAN 0.015263132
SILFLGK_389.2_201.1 THBG_HUMAN 0.015265233 TVQAVLTVPK_528.3_428.3
PEDF_HUMAN 0.015344052 VEPLYELVTATDFAYSSTVR_754.4_712.4 CO8B_HUMAN
0.015451068 FSLVSGWGQLLDR_493.3_447.3 FA7_HUMAN 0.015510454
GWVTDGFSSLK_598.8_854.4 APOC3_HUMAN 0.01610797 LSETNR_360.2_519.3
PSG1_HUMAN 0.016433362 TQILEWAAER_608.8_632.3 EGLN_HUMAN 0.01644844
SETEIHQGFQHLHQLFAK_717.4_318.1 CBG_HUMAN 0.016720367
TNLESILSYPK_632.8_936.5 IC1_HUMAN 0.017314185
TNLESILSYPK_632.8_807.5 IC1_HUMAN 0.017593786 AYSDLSR_406.2_375.2
SAMP_HUMAN 0.018531348 YEVQGEVFTKPQLWP_911.0_392.2 CRP_HUMAN
0.019111323 AYSDLSR_406.2_577.3 SAMP_HUMAN 0.019271266
QALEEFQK_496.8_680.3 CO8B_HUMAN 0.019429489 APLTKPLK_289.9_398.8
CRP_HUMAN 0.020110081 FQPTLLTLPR_593.4_276.1 IC1_HUMAN 0.020114306
ITQDAQLK_458.8_803.4 CBG_HUMAN 0.020401782 AVLHIGEK_289.5_292.2
THBG_HUMAN 0.02056597 ANDQYLTAAALHNLDEAVK_686.4_317.2 IL1A_HUMAN
0.020770124 VGEYSLYIGR_578.8_708.4 SAMP_HUMAN 0.021126414
TLYSSSPR_455.7_533.3 IC1_HUMAN 0.021306106 VEHSDLSFSK_383.5_234.1
B2MG_HUMAN 0.021640643 HELTDEELQSLFTNFANVVDK_817.1_906.5 AFAM_HUMAN
0.021921609 TLYSSSPR_455.7_696.3 IC1_HUMAN 0.022196181
GYVIIKPLVWV_643.9_854.6 SAMP_HUMAN 0.023126336
DEIPHNDIALLK_459.9_260.2 HABP2_HUMAN 0.023232158
ILILPSVTR_506.3_785.5 PSGx_HUMAN 0.023519909
WNFAYWAAHQPWSR_607.3_545.3 PRG2_HUMAN 0.023697087
FQPTLLTLPR_593.4_712.5 IC1_HUMAN 0.023751959
AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 GELS_HUMAN 0.024262721
DEIPHNDIALLK_459.9_510.8 HABP2_HUMAN 0.024414348
GDSGGAFAVQDPNDK_739.3_716.3 C1S_HUMAN 0.025075028
FLNWIK_410.7_561.3 HABP2_HUMAN 0.025649617 APLTKPLK_289.9_357.2
CRP_HUMAN 0.025961162 ALDLSLK_380.2_185.1 ITIH3_HUMAN 0.026233504
GWVTDGFSSLK_598.8_953.5 APOC3_HUMAN 0.026291884
SETEIHQGFQHLHQLFAK_717.4_447.2 CBG_HUMAN 0.026457136
GDSGGAFAVQDPNDK_739.3_473.2 C1S_HUMAN 0.02727457
YEVQGEVFTKPQLWP_911.0_293.1 CRP_HUMAN 0.028244448
HVVQLR_376.2_614.4 IL6RA_HUMAN 0.028428028 DTDTGALLFIGK_625.8_818.5
PEDF_HUMAN 0.028773557 EVPLSALTNILSAQLISHWK_740.8_996.6 PAI1_HUMAN
0.029150774 AFTECCVVASQLR_770.9_574.3 CO5_HUMAN 0.029993325
TLAFVR_353.7_492.3 FA7_HUMAN 0.030064307 LWAYLTIQELLAK_781.5_300.2
ITIH1_HUMAN 0.030368674 DEIPHNDIALLK_459.9_245.1 HABP2_HUMAN
0.031972082 AGLLRPDYALLGHR_518.0_369.2 PGRP2_HUMAN 0.032057409
AVYEAVLR_460.8_587.4 PEPD_HUMAN 0.032527521 LPNNVLQEK_527.8_844.5
AFAM_HUMAN 0.033807082 GAVHVVVAETDYQSFAVLYLER_822.8_580.3
CO8G_HUMAN 0.034370139 WNFAYWAAHQPWSR_607.3_673.3 PRG2_HUMAN
0.0349737 EAQLPVIENK_570.8_329.2 PLMN_HUMAN 0.035304322
VQEAHLTEDQIFYFPK_655.7_701.4 CO8G_HUMAN 0.035704382
AFIQLWAFDAVK_704.9_836.4 AMBP_HUMAN 0.035914532
SGFSFGFK_438.7_585.3 CO8B_HUMAN 0.037168221 SGFSFGFK_438.7_732.4
CO8B_HUMAN 0.040182596 DADPDTFFAK_563.8_302.1 AFAM_HUMAN
0.041439744
EAQLPVIENK_570.8_699.4 PLMN_HUMAN 0.041447675
IIGGSDADIK_494.8_260.2 C1S_HUMAN 0.041683256 AVLTIDEK_444.8_718.4
A1AT_HUMAN 0.043221658 SEPRPGVLLR_375.2_654.4 FA7_HUMAN 0.044079127
YHFEALADTGISSEFYDNANDLLSK_940.8_874.5 CO8A_HUMAN 0.045313634
HFQNLGK_422.2_527.2 AFAM_HUMAN 0.047118971
LEQGENVFLQATDK_796.4_822.4 C1QB_HUMAN 0.047818928
NTVISVNPSTK_580.3_732.4 VCAM1_HUMAN 0.048102262
YYGYTGAFR_549.3_551.3 TRFL_HUMAN 0.048331316
ISLLLIESWLEPVR_834.5_500.3 CSH_HUMAN 0.049561581 LQVLGK_329.2_416.3
A2GL_HUMAN 0.049738493
TABLE-US-00059 TABLE 58 1/38 Univariate p-values for Peak Area
Ratios (<37 vs >37 weeks) UniProt_ID Transition pvalue
SHBG_HUMAN IALGGLLFPASNLR_481.3_657.4 0.006134652 SHBG_HUMAN
IALGGLLFPASNLR_481.3_412.3 0.019049498 APOC3_HUMAN
DALSSVQESQVAQQAR_573.0_672.4 0.020688543 THBG_HUMAN
AVLHIGEK_289.5_292.2 0.0291698 PSG9_HUMAN
DVLLLVHNLPQNLPGYFWYK_810.4_960.5 0.033518454 APOC3_HUMAN
DALSSVQESQVAQQAR_573.0_502.3 0.043103265 PSG9_HUMAN
LFIPQITR_494.3_614.4 0.04655948
TABLE-US-00060 TABLE 59 Univariate p-values for Peak Area Ratios
(<37 vs >40 weeks) UniProt_ID Transition pvalue APOC3_HUMAN
DALSSVQESQVAQQAR_573.0_672.4 0.011174438 APOC3_HUMAN
DALSSVQESQVAQQAR_573.0_502.3 0.015231617 PSG9_HUMAN
LFIPQITR_494.3_614.4 0.018308413 PSG9_HUMAN LFIPQITR_494.3_727.4
0.027616871 PSG9_HUMAN DVLLLVHNLPQNLPGYFWYK_810.4_960.5 0.028117582
THBG_HUMAN AVLHIGEK_289.5_292.2 0.038899107 CO6_HUMAN
ALNHLPLEYNSALYSR_621.0_696.4 0.040662269 ENPP2_HUMAN
TYLHTYESEI_628.3_908.4 0.044545826
TABLE-US-00061 TABLE 60 Univariate p-values for Peak Area Ratios in
Time to Birth Linear Model UniProt_ID Transition pvalue ADA12_HUMAN
FGFGGSTDSGPIR_649.3_946.5 5.85E-27 ADA12_HUMAN
FGFGGSTDSGPIR_649.3_745.4 2.65E-24 PSG4_HUMAN TLFIFGVTK_513.3_215.1
1.07E-20 PSG4_HUMAN TLFIFGVTK_513.3_811.5 2.32E-20 PSGx_HUMAN
ILILPSVTR_506.3_785.5 8.25E-16 PSGx_HUMAN ILILPSVTR_506.3_559.3
9.72E-16 PSG1_HUMAN FQLPGQK_409.2_429.2 1.29E-12 PSG11_HUMAN
LFIPQITPK_528.8_261.2 2.11E-12 PSG1_HUMAN FQLPGQK_409.2_276.1
2.33E-12 PSG11_HUMAN LFIPQITPK_528.8_683.4 3.90E-12 PSG6_HUMAN
SNPVTLNVLYGPDLPR_585.7_817.4 5.71E-12 PSG6_HUMAN
SNPVTLNVLYGPDLPR_585.7_654.4 1.82E-11 VGFR3_HUMAN
SGVDLADSNQK_567.3_662.3 4.57E-11 INHBE_HUMAN ALVLELAK_428.8_331.2
1.04E-08 PSG2_HUMAN IHPSYTNYR_384.2_452.2 6.27E-08 PSG9_HUMAN
LFIPQITR_494.3_727.4 1.50E-07 VGFR3_HUMAN SGVDLADSNQK_567.3_591.3
2.09E-07 PSG9_HUMAN LFIPQITR_494.3_614.4 2.71E-07 PSG9_HUMAN
DVLLLVHNLPQNLPGYFWYK_810.4_960.5 3.10E-07 PSG2_HUMAN
IHPSYTNYR_384.2_338.2 2.55E-06 ITIH3_HUMAN
LIQDAVTGLTVNGQITGDK_972.0_640.4 2.76E-06 ENPP2_HUMAN
TYLHTYESEI_628.3_908.4 2.82E-06 ENPP2_HUMAN
WWGGQPLWITATK_772.4_373.2 3.75E-06 PSG9_HUMAN
DVLLLVHNLPQNLPGYFWYK_810.4_328.2 3.94E-06 B2MG_HUMAN
VEHSDLSFSK_383.5_468.2 5.42E-06 ENPP2_HUMAN
WWGGQPLWITATK_772.4_929.5 7.93E-06 ANGT_HUMAN
ALQDQLVLVAAK_634.9_289.2 1.04E-05 B2MG_HUMAN VNHVTLSQPK_374.9_244.2
1.46E-05 AFAM_HUMAN LPNNVLQEK_527.8_730.4 1.50E-05 AFAM_HUMAN
LPNNVLQEK_527.8_844.5 1.98E-05 THBG_HUMAN AVLHIGEK_289.5_292.2
2.15E-05 ENPP2_HUMAN TYLHTYESEI_628.3_515.3 2.17E-05 IL12B_HUMAN
DIIKPDPPK_511.8_342.2 3.31E-05 AFAM_HUMAN DADPDTFFAK_563.8_302.1
6.16E-05 THBG_HUMAN AVLHIGEK_289.5_348.7 8.34E-05 PSG9_HUMAN
DVLLLVHNLPQNLPGYFWYK_810.4_215.1 0.000104442 B2MG_HUMAN
VEHSDLSFSK_383.5_234.1 0.000140786 TRFL_HUMAN YYGYTGAFR_549.3_450.3
0.000156543 HEMO_HUMAN QGHNSVFLIK_381.6_260.2 0.000164578
A1BG_HUMAN LLELTGPK_435.8_227.2 0.000171113 CO6_HUMAN
ALNHLPLEYNSALYSR_621.0_696.4 0.000242116 CO6_HUMAN
ALNHLPLEYNSALYSR_621.0_538.3 0.00024681 ALS_HUMAN
IRPHTFTGLSGLR_485.6_432.3 0.000314359 ITIH2_HUMAN
LSNENHGIAQR_413.5_544.3 0.0004877 PEDF_HUMAN TVQAVLTVPK_528.3_855.5
0.000508174 AFAM_HUMAN HFQNLGK_422.2_527.2 0.000522139 FLNA_HUMAN
TGVAVNKPAEFTVDAK_549.6_258.1 0.000594403 ANGT_HUMAN
ALQDQLVLVAAK_634.9_956.6 0.000640673 AFAM_HUMAN HFQNLGK_422.2_285.1
0.000718763 HGFA_HUMAN LHKPGVYTR_357.5_692.4 0.000753293 HGFA_HUMAN
LHKPGVYTR_357.5_479.3 0.000909298 HABP2_HUMAN FLNWIK_410.7_561.3
0.001282014 FETUA_HUMAN HTLNQIDEVK_598.8_951.5 0.001389792
AFAM_HUMAN DADPDTFFAK_563.8_825.4 0.001498237 B2MG_HUMAN
VNHVTLSQPK_374.9_459.3 0.001559862 ALS_HUMAN
IRPHTFTGLSGLR_485.6_545.3 0.001612361 A1BG_HUMAN
LLELTGPK_435.8_644.4 0.002012656 F13B_HUMAN LIENGYFHPVK_439.6_343.2
0.00275216 ITIH2_HUMAN LSNENHGIAQR_413.5_519.8 0.00356561
APOC3_HUMAN DALSSVQESQVAQQAR_573.0_672.4 0.00392745 F13B_HUMAN
LIENGYFHPVK_439.6_627.4 0.00434836 PEDF_HUMAN
TVQAVLTVPK_528.3_428.3 0.00482765 PLMN_HUMAN YEFLNGR_449.7_293.1
0.007325436 HEMO_HUMAN QGHNSVFLIK_381.6_520.4 0.009508516
FETUA_HUMAN HTLNQIDEVK_598.8_958.5 0.010018936 CO5_HUMAN
LQGTLPVEAR_542.3_842.5 0.011140661 PLMN_HUMAN YEFLNGR_449.7_606.3
0.01135322 CO5_HUMAN TLLPVSKPEIR_418.3_288.2 0.015045275
HABP2_HUMAN FLNWIK_410.7_560.3 0.01523134 APOC3_HUMAN
DALSSVQESQVAQQAR_573.0_502.3 0.01584708 CO5_HUMAN
LQGTLPVEAR_542.3_571.3 0.017298064 CFAB_HUMAN DISEVVTPR_508.3_472.3
0.021743221 CERU_HUMAN TTIEKPVWLGFLGPIIK_638.0_640.4 0.02376225
CO8G_HUMAN SLPVSDSVLSGFEQR_810.9_723.3 0.041150397 CO8G_HUMAN
FLQEQGHR_338.8_497.3 0.042038143 CO5_HUMAN VFQFLEK_455.8_811.4
0.043651929 CO8B_HUMAN QALEEFQK_496.8_680.3 0.04761631
TABLE-US-00062 TABLE 61 Univariate p-values for Peak Area Ratios in
Gestation Age at Birth Linear Model UniProt_ID Transition pvalue
PSG9_HUMAN DVLLLVHNLPQNLPGYFWYK_810.4_960.5 0.000431547 B2MG_HUMAN
VEHSDLSFSK_383.5_468.2 0.000561148 PSG9_HUMAN
DVLLLVHNLPQNLPGYFWYK_810.4_328.2 0.000957509 ENPP2_HUMAN
TYLHTYESEI_628.3_908.4 0.001058809 THBG_HUMAN AVLHIGEK_289.5_292.2
0.001180484 ENPP2_HUMAN WWGGQPLWITATK_772.4_373.2 0.001524983
PSG9_HUMAN LFIPQITR_494.3_614.4 0.001542932 ENPP2_HUMAN
WWGGQPLWITATK_772.4_929.5 0.002047607 ENPP2_HUMAN
TYLHTYESEI_628.3_515.3 0.003087492 PSG9_HUMAN LFIPQITR_494.3_727.4
0.00477154 PSG9_HUMAN DVLLLVHNLPQNLPGYFWYK_810.4_215.1 0.004824351
THBG_HUMAN AVLHIGEK_289.5_348.7 0.006668084 AFAM_HUMAN
LPNNVLQEK_527.8_730.4 0.006877647 ADA12_HUMAN
FGFGGSTDSGPIR_649.3_745.4 0.011738104 PEDF_HUMAN
TVQAVLTVPK_528.3_855.5 0.013349511 A1BG_HUMAN LLELTGPK_435.8_227.2
0.015793885 ITIH3_HUMAN ALDLSLK_380.2_185.1 0.016080436 ADA12_HUMAN
FGFGGSTDSGPIR_649.3_946.5 0.017037089 B2MG_HUMAN
VEHSDLSFSK_383.5_234.1 0.017072093 CO6_HUMAN
ALNHLPLEYNSALYSR_621.0_696.4 0.024592775 TRFL_HUMAN
YYGYTGAFR_549.3_450.3 0.030890831 AFAM_HUMAN DADPDTFFAK_563.8_302.1
0.033791429 CO6_HUMAN ALNHLPLEYNSALYSR_621.0_538.3 0.034865341
AFAM_HUMAN LPNNVLQEK_527.8_844.5 0.039880594 PEDF_HUMAN
TVQAVLTVPK_528.3_428.3 0.040854402 PLMN_HUMAN
EAQLPVIENK_570.8_329.2 0.041023812 LBP_HUMAN
ITLPDFTGDLR_624.3_920.5 0.042276813 CO8G_HUMAN
VQEAHLTEDQIFYFPK_655.7_701.4 0.042353851 PLMN_HUMAN
YEFLNGR_449.7_606.3 0.04416504 B2MG_HUMAN VNHVTLSQPK_374.9_459.3
0.045458409 CFAB_HUMAN DISEVVTPR_508.3_472.3 0.046493405
INHBE_HUMAN ALVLELAK_428.8_331.2 0.04789353
TABLE-US-00063 TABLE 62 Random Forest Importance Values Using
Adjusted Peak Areas Transition Rank Importance
INHBE_ALVLELAK_428.8_672.4 1 2964.951571
EGLN_TQILEWAAER_608.8_761.4 2 1218.3406 FA7_SEPRPGVLLR_375.2_654.4
3 998.92897 CBG_ITQDAQLK_458.8_702.4 4 930.9931102
ITIH3_ALDLSLK_380.2_185.1 5 869.6315408
ENPP2_WWGGQPLWITATK_772.4_929.5 6 768.9182114
CBG_ITQDAQLK_458.8_803.4 7 767.8940452 PSG1_LSETNR_360.2_519.3 8
714.6160065 CAA60698_LEPLYSASGPGLRPLVIK_637.4_834.5 9 713.4086612
INHBC_LDFHFSSDR_375.2_611.3 11 681.2442909 CBG_QINSYVK_426.2_610.3
12 674.3363415 LBP_GLQYAAQEGLLALQSELLR_1037.1_858.5 13 603.197751
A1BG_LLELTGPK_435.8_644.4 14 600.9902818 CO6_DLHLSDVFLK_396.2_366.2
15 598.8214342 VCAM1_TQIDSPLSGK_523.3_816.5 16 597.4038769
LRP1_NAVVQGLEQPHGLVVHPLR_688.4_285.2 17 532.0500081
CBG_QINSYVK_426.2_496.3 18 516.5575201
CO6_ENPAVIDFELAPIVDLVR_670.7_811.5 19 501.4669261
ADA12_FGFGGSTDSGPIR_649.3_745.4 20 473.5510333
CO6_DLHLSDVFLK_396.2_260.2 21 470.5473702
ENPP2_TYLHTYESEI_628.3_908.4 22 444.7580726
A1BG_LLELTGPK_435.8_227.2 23 444.696292
FRIH_QNYHQDSEAAINR_515.9_544.3 24 439.2648872
ENPP2_TEFLSNYLTNVDDITLVPGTLGR_846.8_600.3 25 389.3769604
CBG_WSAGLTSSQVDLYIPK_883.0_515.3 26 374.0749768
C1QC_FQSVFTVTR_542.8_623.4 27 370.6957977
GELS_DPDQTDGLGLSYLSSHIANVER_796.4_456.2 28 353.1176588
A1BG_ATWSGAVLAGR_544.8_643.4 29 337.4580124
APOA1_AKPALEDLR_506.8_813.5 30 333.5742035
ENPP2_TYLHTYESEI_628.3_515.3 31 322.6339162
PEPD_AVYEAVLR_460.8_750.4 32 321.4377907
TIMP1_GFQALGDAADIR_617.3_717.4 33 310.0997949
ADA12_LIEIANHVDK_384.6_498.3 34 305.8803542
PGRP2_WGAAPYR_410.7_577.3 35 303.5539874 PSG9_LFIPQITR_494.3_614.4
36 300.7877317 HABP2_FLNWIK_410.7_560.3 37 298.3363186
CBG_WSAGLTSSQVDLYIPK_883.0_357.2 38 297.2474385
PSG2_IHPSYTNYR_384.2_452.2 39 292.6203405
PSG5_LSIPQITTK_500.8_800.5 40 290.2023364 HABP2_FLNWIK_410.7_561.3
41 289.5092933 CO6_SEYGAALAWEK_612.8_788.4 42 287.7634114
ADA12_LIEIANHVDK_384.6_683.4 43 286.5047372
EGLN_TQILEWAAER_608.8_632.3 44 284.5138846
CO6_ENPAVIDFELAPIVDLVR_670.7_601.4 45 273.5146272
FA7_FSLVSGWGQLLDR_493.3_447.3 46 271.7850098
ITIH3_ALDLSLK_380.2_575.3 47 269.9425709
ADA12_FGFGGSTDSGPIR_649.3_946.5 48 264.5698225
FETUA_AALAAFNAQNNGSNFQLEEISR_789.1_746.4 49 247.4728828
FBLN1_AITPPHPASQANIIFDITEGNLR_825.8_459.3 50 246.572102
TSP1_FVFGTTPEDILR_697.9_843.5 51 245.0459575
VCAM1_NTVISVNPSTK_580.3_732.4 52 240.576729
ENPP2_TEFLSNYLTNVDDITLVPGTLGR_846.8_699.4 53 240.1949512
FBLN3_ELPQSIVYK_538.8_409.2 55 233.6825304
ACTB_VAPEEHPVLLTEAPLNPK_652.0_892.5 56 226.9772749
TSP1_FVFGTTPEDILR_697.9_742.4 57 224.4627393
PLMN_EAQLPVIENK_570.8_699.4 58 221.4663735
C1S_IIGGSDADIK_494.8_260.2 59 218.069476
IL1A_ANDQYLTAAALHNLDEAVK_686.4_317.2 60 216.5531949
PGRP2_WGAAPYR_410.7_634.3 61 211.0918302 PSG5_LSIPQITTK_500.8_687.4
62 208.7871461 PSG6_SNPVTLNVLYGPDLPR_585.7_654.4 63 207.9294937
PRG2_WNFAYWAAHQPWSR_607.3_545.3 64 202.9494031
CXCL2_CQCLQTLQGIHLK_13p8RT_533.6_567.4 65 202.9051326
CXCL2_CQCLQTLQGIHLK_13p48RT_533.6_695.4 66 202.6561548
G6PE_LLDFEFSSGR_585.8_553.3 67 201.004611 GELS_TASDFITK_441.7_710.4
68 200.2704809 B2MG_VEHSDLSFSK_383.5_468.2 69 199.880987
CO8B_IPGIFELGISSQSDR_809.9_849.4 70 198.7563875
PSG8_LQLSETNR_480.8_606.3 71 197.6739966
LBP_GLQYAAQEGLLALQSELLR_1037.1_929.5 72 197.4094851
AFAM_LPNNVLQEK_527.8_844.5 73 196.8123228 MAGE 74 196.2410502
PSG2_IHPSYTNYR_384.2_338.2 75 196.2410458 PSG9_LFIPQITR_494.3_727.4
76 193.5329266 TFR1_YNSQLLSFVR_613.8_734.5 77 193.2711994
C1R_QRPPDLDTSSNAVDLLFFTDESGDSR_961.5_866.3 78 193.0625419
PGH1_ILPSVPK_377.2_264.2 79 190.0504508 FA7_SEPRPGVLLR_375.2_454.3
80 188.2718422 FA7_TLAFVR_353.7_274.2 81 187.6895294
PGRP2_DGSPDVTTADIGANTPDATK_973.5_844.4 82 185.6017519
C1S_IIGGSDADIK_494.8_762.4 83 184.5985543
PEPD_VPLALFALNR_557.3_620.4 84 184.3962957
C1S_EDTPNSVWEPAK_686.8_630.3 85 179.2043504
CHL1_TAVTANLDIR_537.3_802.4 86 174.9866792
CHL1_VIAVNEVGR_478.8_744.4 88 172.2053147
SDF1_ILNTPNCALQIVAR_791.9_341.2 89 171.4604557
PAI1_EVPLSALTNILSAQLISHWK_740.8_996.6 90 169.5635635
AMBP_AFIQLWAFDAVK_704.9_650.4 91 169.2124477
G6PE_LLDFEFSSGR_585.8_944.4 92 168.2398598 THBG_SILFLGK_389.2_577.4
93 166.3110206 PRDX2_GLFIIDGK_431.8_545.3 94 164.3125132
ENPP2_WWGGQPLWITATK_772.4_373.2 95 163.4011689
VGFR3_SGVDLADSNQK_567.3_662.3 96 162.8822352
C1S_EDTPNSVWEPAK_686.8_315.2 97 161.6140915
AFAM_DADPDTFFAK_563.8_302.1 98 159.5917449
CBG_SETEIHQGFQHLHQLFAK_717.4_447.2 99 156.1357404
C1S_LLEVPEGR_456.8_686.4 100 155.1763293 PTGDS_GPGEDFR_389.2_623.3
101 154.9205208 ITIH2_IYLQPGR_423.7_329.2 102 154.6552717
FA7_TLAFVR_353.7_492.3 103 152.5009422
FA7_FSLVSGWGQLLDR_493.3_403.2 104 151.9971204
SAMP_VGEYSLYIGR_578.8_871.5 105 151.4738449
APOH_EHSSLAFWK_552.8_267.1 106 151.0052645
PGRP2_AGLLRPDYALLGHR_518.0_595.4 107 150.4149907
C1QC_FNAVLTNPQGDYDTSTGK_964.5_333.2 108 149.2592827
PGRP2_AGLLRPDYALLGHR_518.0_369.2 109 147.3609354
PGRP2_TFTLLDPK_467.8_686.4 111 145.2145223
CO5_TDAPDLPEENQAR_728.3_843.4 112 144.5213118
THRB_ELLESYIDGR_597.8_839.4 113 143.924639
GELS_DPDQTDGLGLSYLSSHIANVER_796.4_328.1 114 142.8936101
TRFL_YYGYTGAFR_549.3_450.3 115 142.8651352
HEMO_QGHNSVFLIK_381.6_260.2 116 142.703845
C1S_GDSGGAFAVQDPNDK_739.3_716.3 117 142.2799122
B1A4H9_AHQLAIDTYQEFR_531.3_450.3 118 138.196407
C1S_SSNNPHSPIVEEFQVPYNK_729.4_261.2 119 136.7868935
HYOU1_LPATEKPVLLSK_432.6_347.2 120 136.1146437
FETA_GYQELLEK_490.3_502.3 121 135.2890322
LRP1_SERPPIFEIR_415.2_288.2 122 134.6569527
CO6_SEYGAALAWEK_612.8_845.5 124 132.8634704
CERU_TTIEKPVWLGFLGPIIK_638.0_844.5 125 132.1047746
IBP1_AQETSGEEISK_589.8_850.4 126 130.934446
SHBG_VVLSSGSGPGLDLPLVLGLPLQLK_791.5_768.5 127 128.2052287
CBG_SETEIHQGFQHLHQLFAK_717.4_318.1 128 127.9873837
A1AT_LSITGTYDLK_555.8_696.4 129 127.658818
PGRP2_DGSPDVTTADIGANTPDATK_973.5_531.3 130 126.5775806
C1QB_LEQGENVFLQATDK_796.4_675.4 131 126.1762726
EGLN_GPITSAAELNDPQSILLR_632.4_826.5 132 125.7658253
IL12B_YENYTSSFFIR_713.8_293.1 133 125.0476631
B2MG_VEHSDLSFSK_383.5_234.1 134 124.9154706
PGH1_AEHPTWGDEQLFQTTR_639.3_765.4 135 124.8913193
INHBE_ALVLELAK_428.8_331.2 136 124.0109276
HYOU1_LPATEKPVLLSK_432.6_460.3 137 123.1900369
CXCL2_CQCLQTLQGIHLK_13p48RT_533.6_567.4 138 122.8800873
PZP_AVGYLITGYQR_620.8_523.3 139 122.4733204
AFAM_IAPQLSTEELVSLGEK_857.5_333.2 140 122.4707849
ICAM1_VELAPLPSWQPVGK_760.9_400.3 141 121.5494206
CHL1_VIAVNEVGR_478.8_284.2 142 119.0877137
APOB_ITENDIQIALDDAK_779.9_632.3 143 118.0222045
SAMP_AYSDLSR_406.2_577.3 144 116.409429
AMBP_AFIQLWAFDAVK_704.9_836.4 145 116.1900846
EGLN_GPITSAAELNDPQSILLR_632.4_601.4 146 115.8438804
LRP1_NAVVQGLEQPHGLVVHPLR_688.4_890.6 147 114.539707
SHBG_VVLSSGSGPGLDLPLVLGLPLQLK_791.5_598.4 148 113.1931134
IBP1_AQETSGEEISK_589.8_979.5 149 112.9902709
PSG6_SNPVTLNVLYGPDLPR_585.7_817.4 150 112.7910917
APOC3_DYWSTVK_449.7_347.2 151 112.544736
C1R_WILTAAHTLYPK_471.9_621.4 152 112.2199708
ANGT_ADSQAQLLLSTVVGVFTAPGLHLK_822.5_983.6 153 111.9634671
PSG9_DVLLLVHNLPQNLPGYFWYK_810.4_328.2 154 111.5743214
A1AT_AVLTIDEK_444.8_605.3 155 111.216651 PSGx_ILILPSVTR_506.3_785.5
156 110.8482935 THRB_ELLESYIDGR_597.8_710.4 157 110.7496103
SHBG_ALALPPLGLAPLLNLWAKPQGR_770.5_256.2 158 110.5091269
PZP_QTLSWTVTPK_580.8_545.3 159 110.4675104
SHBG_ALALPPLGLAPLLNLWAKPQGR_770.5_457.3 160 110.089808
PSG4_TLFIFGVTK_513.3_811.5 161 109.9039967 PLMN_YEFLNGR_449.7_293.1
162 109.6880397 PEPD_AVYEAVLR_460.8_587.4 163 109.3697285
PLMN_LSSPAVITDK_515.8_830.5 164 108.963353
FINC_SYTITGLQPGTDYK_772.4_352.2 165 108.452612
C1R_WILTAAHTLYPK_471.9_407.2 166 107.8348417
CHL1_TAVTANLDIR_537.3_288.2 167 107.7278897
TENA_AVDIPGLEAATPYR_736.9_286.1 168 107.6166195
CRP_YEVQGEVFTKPQLWP_911.0_293.1 169 106.9739589
APOB_SVSLPSLDPASAK_636.4_885.5 170 106.5901668
PRDX2_SVDEALR_395.2_488.3 171 106.2325046
CO8A_YHFEALADTGISSEFYDNANDLLSK_940.8_301.1 172 105.8963287
C1QC_FQSVFTVTR_542.8_722.4 173 105.4338742
PSGx_ILILPSVTR_506.3_559.3 174 105.1942655
VCAM1_TQIDSPLSGK_523.3_703.4 175 105.0091767
VCAM1_NTVISVNPSTK_580.3_845.5 176 104.8754444
CSH_ISLLLIESWLEPVR_834.5_500.3 177 104.6158295
HGFA_EALVPLVADHK_397.9_439.8 178 104.3383142
CGB1_CRPINATLAVEK_457.9_660.4 179 104.3378072
APOB_IEGNLIFDPNNYLPK_874.0_414.2 180 103.9849346
C1QB_LEQGENVFLQATDK_796.4_822.4 181 103.9153207
APOH_EHSSLAFWK_552.8_838.4 182 103.9052103
CO5_LQGTLPVEAR_542.3_842.5 183 103.1061869
SHBG_IALGGLLFPASNLR_481.3_412.3 184 102.2490294
B2MG_VNHVTLSQPK_374.9_459.3 185 102.1204362
APOA2_SPELQAEAK_486.8_659.4 186 101.9166647
FLNA_TGVAVNKPAEFTVDAK_549.6_258.1 187 101.5207852
PLMN_YEFLNGR_449.7_606.3 188 101.2531011
TABLE-US-00064 TABLE 63 Random Forest Importance Values Using Peak
Area Ratios Variable Rank Importance HABP2_FLNWIK_410.7_561.3 1
3501.905733 ADA12_FGFGGSTDSGPIR_649.3_946.5 2 3136.589992
A1BG_LLELTGPK_435.8_227.2 3 2387.891934 B2MG_VEHSDLSFSK_383.5_234.1
4 1431.31771 ADA12_FGFGGSTDSGPIR_649.3_745.4 5 1400.917331
B2MG_VEHSDLSFSK_383.5_468.2 6 1374.453629
APOB_IEGNLIFDPNNYLPK_874.0_414.2 7 1357.812445
PSG9_DVLLLVHNLPQNLPGYFWYK_810.4_960.5 8 1291.934596
A1BG_LLELTGPK_435.8_644.4 9 1138.712941 ITIH3_ALDLSLK_380.2_185.1
10 1137.127027 ENPP2_TYLHTYESEI_628.3_908.4 11 1041.036693
IL12B_YENYTSSFFIR_713.8_293.1 12 970.1662913
ENPP2_WWGGQPLWITATK_772.4_373.2 13 953.0631062
ENPP2_TYLHTYESEI_628.3_515.3 14 927.3512901
PSG9_LFIPQITR_494.3_614.4 15 813.9965357 MAGE 16 742.2425022
ENPP2_WWGGQPLWITATK_772.4_929.5 17 731.5206413
CERU_TTIEKPVWLGFLGPIIK_638.0_640.4 18 724.7745695
ITIH3_ALDLSLK_380.2_575.3 19 710.1982467 PSG2_IHPSYTNYR_384.2_452.2
20 697.4750893 ITIH1_LWAYLTIQELLAK_781.5_371.2 21 644.7416886
INHBE_ALVLELAK_428.8_331.2 22 643.008853 HGFA_LHKPGVYTR_357.5_692.4
23 630.8698445 TRFL_YYGYTGAFR_549.3_450.3 24 609.5866675
THBG_AVLHIGEK_289.5_348.7 25 573.9320948 GELS_TASDFITK_441.7_710.4
26 564.3288862 PSG9_LFIPQITR_494.3_727.4 27 564.1749327
VGFR3_SGVDLADSNQK_567.3_662.3 28 563.8087791
INHA_TTSDGGYSFK_531.7_860.4 29 554.210214
PSG9_DVLLLVHNLPQNLPGYFWYK_810.4_328.2 30 545.1743627
HYOU1_LPATEKPVLLSK_432.6_347.2 31 541.6208032
CO8G_VQEAHLTEDQIFYFPK_655.7_701.4 32 541.3193428 BMI 33 540.5028818
HGFA_LHKPGVYTR_357.5_479.3 34 536.6051948
PSG2_IHPSYTNYR_384.2_338.2 35 536.5363489
GELS_AQPVQVAEGSEPDGFWEALGGK_758.0_623.4 36 536.524931
PSG6_SNPVTLNVLYGPDLPR_585.7_654.4 37 520.108646
HABP2_FLNWIK_410.7_560.3 38 509.0707814 PGH1_ILPSVPK_377.2_527.3 39
503.593718 HYOU1_LPATEKPVLLSK_432.6_460.3 40 484.047422
CO6_ALNHLPLEYNSALYSR_621.0_696.4 41 477.8773179
INHBE_ALVLELAK_428.8_672.4 42 459.1998276
PLMN_LSSPAVITDK_515.8_743.4 43 452.9466414
PSG9_DVLLLVHNLPQNLPGYFWYK_810.4_215.1 44 431.8528248
BGH3_LTLLAPLNSVFK_658.4_875.5 45 424.2540315
AFAM_LPNNVLQEK_527.8_730.4 46 421.4953221
ITIH2_LSNENHGIAQR_413.5_519.8 47 413.1231437
GELS_TASDFITK_441.7_781.4 48 404.2679723 FETUA_AHYDLR_387.7_566.3
49 400.4711207 CERU_TTIEKPVWLGFLGPIIK_638.0_844.5 50 396.2873451
PSGx_ILILPSVTR_506.3_785.5 51 374.5672526
APOB_SVSLPSLDPASAK_636.4_885.5 52 371.1416438
FLNA_TGVAVNKPAEFTVDAK_549.6_258.1 53 370.4175588
PLMN_YEFLNGR_449.7_606.3 54 367.2768078 PSGx_ILILPSVTR_506.3_559.3
55 365.7704321
[0191] From the foregoing description, it will be apparent that
variations and modifications can be made to the invention described
herein to adopt it to various usages and conditions. Such
embodiments are also within the scope of the following claims.
[0192] The recitation of a listing of elements in any definition of
a variable herein includes definitions of that variable as any
single element or combination (or subcombination) of listed
elements. The recitation of an embodiment herein includes that
embodiment as any single embodiment or in combination with any
other embodiments or portions thereof.
[0193] All patents and publications mentioned in this specification
are herein incorporated by reference to the same extent as if each
independent patent and publication was specifically and
individually indicated to be incorporated by reference.
Sequence CWU 1
1
1069113PRTHomo sapiens 1Ala Phe Thr Glu Cys Cys Val Val Ala Ser Gln
Leu Arg 1 5 10 210PRTHomo sapiens 2Glu Leu Leu Glu Ser Tyr Ile Asp
Gly Arg 1 5 10 311PRTHomo sapiens 3Ile Thr Leu Pro Asp Phe Thr Gly
Asp Leu Arg 1 5 10 46PRTHomo sapiens 4Phe Leu Asn Trp Ile Lys 1 5
513PRTHomo sapiens 5Phe Gly Phe Gly Gly Ser Thr Asp Ser Gly Pro Ile
Arg 1 5 10 68PRTHomo sapiens 6Leu Leu Glu Leu Thr Gly Pro Lys 1 5
710PRTHomo sapiens 7Val Glu His Ser Asp Leu Ser Phe Ser Lys 1 5 10
815PRTHomo sapiens 8Ile Glu Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr
Leu Pro Lys 1 5 10 15 98PRTHomo sapiens 9Ala Leu Val Leu Glu Leu
Ala Lys 1 5 1010PRTHomo sapiens 10Thr Gln Ile Leu Glu Trp Ala Ala
Glu Arg 1 5 10 1120PRTHomo sapiens 11Asp Val Leu Leu Leu Val His
Asn Leu Pro Gln Asn Leu Pro Gly Tyr 1 5 10 15 Phe Trp Tyr Lys 20
1210PRTHomo sapiens 12Ser Glu Pro Arg Pro Gly Val Leu Leu Arg 1 5
10 138PRTHomo sapiens 13Ile Thr Gln Asp Ala Gln Leu Lys 1 5
147PRTHomo sapiens 14Ala Leu Asp Leu Ser Leu Lys 1 5 1513PRTHomo
sapiens 15Trp Trp Gly Gly Gln Pro Leu Trp Ile Thr Ala Thr Lys 1 5
10 166PRTHomo sapiens 16Leu Ser Glu Thr Asn Arg 1 5 1713PRTHomo
sapiens 17Thr Asp Ala Pro Asp Leu Pro Glu Glu Asn Gln Ala Arg 1 5
10 188PRTHomo sapiens 18Ser Phe Arg Pro Phe Val Pro Arg 1 5
1914PRTHomo sapiens 19Leu Glu Gln Gly Glu Asn Val Phe Leu Gln Ala
Thr Asp Lys 1 5 10 2012PRTHomo sapiens 20Glu Thr Ala Ala Ser Leu
Leu Gln Ala Gly Tyr Lys 1 5 10 218PRTHomo sapiens 21Val Thr Gly Trp
Gly Asn Leu Lys 1 5 2210PRTHomo sapiens 22Glu Ala Gln Leu Pro Val
Ile Glu Asn Lys 1 5 10 238PRTHomo sapiens 23Phe Leu Gln Glu Gln Gly
His Arg 1 5 248PRTHomo sapiens 24Ile Arg Pro Phe Phe Pro Gln Gln 1
5 2511PRTHomo sapiens 25Thr Leu Leu Pro Val Ser Lys Pro Glu Ile Arg
1 5 10 2610PRTHomo sapiens 26Leu Ser Ser Pro Ala Val Ile Thr Asp
Lys 1 5 10 2715PRTHomo sapiens 27Tyr Glu Val Gln Gly Glu Val Phe
Thr Lys Pro Gln Leu Trp Pro 1 5 10 15 2810PRTHomo sapiens 28Leu Gln
Gly Thr Leu Pro Val Glu Ala Arg 1 5 10 298PRTHomo sapiens 29Val Arg
Pro Gln Gln Leu Val Lys 1 5 307PRTHomo sapiens 30Ile Glu Glu Ile
Ala Ala Lys 1 5 3116PRTHomo sapiens 31Val Gln Glu Ala His Leu Thr
Glu Asp Gln Ile Phe Tyr Phe Pro Lys 1 5 10 15 3214PRTHomo sapiens
32Ile Ser Leu Leu Leu Ile Glu Ser Trp Leu Glu Pro Val Arg 1 5 10
3312PRTHomo sapiens 33Ala Leu Gln Asp Gln Leu Val Leu Val Ala Ala
Lys 1 5 10 347PRTHomo sapiens 34Tyr Glu Phe Leu Asn Gly Arg 1 5
3518PRTHomo sapiens 35Thr Pro Ser Ala Ala Tyr Leu Trp Val Gly Thr
Gly Ala Ser Glu Ala 1 5 10 15 Glu Lys 3613PRTHomo sapiens 36Thr Ala
Thr Ser Glu Tyr Gln Thr Phe Phe Asn Pro Arg 1 5 10 378PRTHomo
sapiens 37Thr Ala Ser Asp Phe Ile Thr Lys 1 5 3818PRTHomo sapiens
38Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln 1
5 10 15 Asn Arg 3910PRTHomo sapiens 39Ile Ile Gly Gly Ser Asp Ala
Asp Ile Lys 1 5 10 407PRTHomo sapiens 40Tyr Thr Thr Glu Ile Ile Lys
1 5 4112PRTHomo sapiens 41Glu Asp Thr Pro Asn Ser Val Trp Glu Pro
Ala Lys 1 5 10 428PRTHomo sapiens 42Leu Tyr Tyr Gly Asp Asp Glu Lys
1 5 438PRTHomo sapiens 43Gly Gly Glu Ile Glu Gly Phe Arg 1 5
4420PRTHomo sapiens 44Asp Gly Ser Pro Asp Val Thr Thr Ala Asp Ile
Gly Ala Asn Thr Pro 1 5 10 15 Asp Ala Thr Lys 20 456PRTHomo sapiens
45Val Glu Ile Asp Thr Lys 1 5 468PRTHomo sapiens 46Ala Val Leu Thr
Ile Asp Glu Lys 1 5 477PRTHomo sapiens 47Phe Ser Val Val Tyr Ala
Lys 1 5 487PRTHomo sapiens 48Tyr Tyr Leu Gln Gly Ala Lys 1 5
4913PRTHomo sapiens 49Glu Glu Asn Phe Tyr Val Asp Glu Thr Thr Val
Val Lys 1 5 10 509PRTHomo sapiens 50Tyr Gly Phe Tyr Thr His Val Phe
Arg 1 5 5110PRTHomo sapiens 51His Thr Leu Asn Gln Ile Asp Glu Val
Lys 1 5 10 5212PRTHomo sapiens 52Ala Phe Ile Gln Leu Trp Ala Phe
Asp Ala Val Lys 1 5 10 538PRTHomo sapiens 53Ser Gly Phe Ser Phe Gly
Phe Lys 1 5 5411PRTHomo sapiens 54Gly Trp Val Thr Asp Gly Phe Ser
Ser Leu Lys 1 5 10 5514PRTHomo sapiens 55Ile Thr Glu Asn Asp Ile
Gln Ile Ala Leu Asp Asp Ala Lys 1 5 10 5620PRTHomo sapiens 56Val
Glu Pro Leu Tyr Glu Leu Val Thr Ala Thr Asp Phe Ala Tyr Ser 1 5 10
15 Ser Thr Val Arg 20 5722PRTHomo sapiens 57Asp Pro Asp Gln Thr Asp
Gly Leu Gly Leu Ser Tyr Leu Ser Ser His 1 5 10 15 Ile Ala Asn Val
Glu Arg 20 5810PRTHomo sapiens 58Val Gly Glu Tyr Ser Leu Tyr Ile
Gly Arg 1 5 10 5915PRTHomo sapiens 59Ser Leu Pro Val Ser Asp Ser
Val Leu Ser Gly Phe Glu Gln Arg 1 5 10 15 6010PRTHomo sapiens 60Asn
Ala Asp Tyr Ser Tyr Ser Val Trp Lys 1 5 10 6110PRTHomo sapiens
61Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys 1 5 10 627PRTHomo sapiens
62Phe Gln Leu Pro Gly Gln Lys 1 5 6311PRTHomo sapiens 63Tyr Gly Leu
Val Thr Tyr Ala Thr Tyr Pro Lys 1 5 10 6418PRTHomo sapiens 64Gly
Ser Phe Ala Leu Ser Phe Pro Val Glu Ser Asp Val Ala Pro Ile 1 5 10
15 Ala Arg 6510PRTHomo sapiens 65Thr Leu Leu Ile Ala Asn Glu Thr
Leu Arg 1 5 10 6622PRTHomo sapiens 66Val Ile Leu Gly Ala His Gln
Glu Val Asn Leu Glu Pro His Val Gln 1 5 10 15 Glu Ile Glu Val Ser
Arg 20 679PRTHomo sapiens 67Asp Ile Ser Glu Val Val Thr Pro Arg 1 5
689PRTHomo sapiens 68Thr Leu Glu Ala Gln Leu Thr Pro Arg 1 5
6911PRTHomo sapiens 69Ala Val Gly Tyr Leu Ile Thr Gly Tyr Gln Arg 1
5 10 7018PRTHomo sapiens 70Phe Asn Ala Val Leu Thr Asn Pro Gln Gly
Asp Tyr Asp Thr Ser Thr 1 5 10 15 Gly Lys 7116PRTHomo sapiens 71Ser
Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 1 5 10
15 7216PRTHomo sapiens 72Ala Leu Asn His Leu Pro Leu Glu Tyr Asn
Ser Ala Leu Tyr Ser Arg 1 5 10 15 7314PRTHomo sapiens 73Gly Gly Glu
Gly Thr Gly Tyr Phe Val Asp Phe Ser Val Arg 1 5 10 749PRTHomo
sapiens 74Gly Ile Val Glu Glu Cys Cys Phe Arg 1 5 757PRTHomo
sapiens 75Phe Ala Phe Asn Leu Tyr Arg 1 5 7623PRTHomo sapiens 76Ala
Ile Thr Pro Pro His Pro Ala Ser Gln Ala Asn Ile Ile Phe Asp 1 5 10
15 Ile Thr Glu Gly Asn Leu Arg 20 7711PRTHomo sapiens 77Glu Pro Gly
Leu Cys Thr Trp Gln Ser Leu Arg 1 5 10 788PRTHomo sapiens 78Ala Val
Tyr Glu Ala Val Leu Arg 1 5 796PRTHomo sapiens 79Ala Trp Val Ala
Trp Arg 1 5 8011PRTHomo sapiens 80Thr Asn Leu Glu Ser Ile Leu Ser
Tyr Pro Lys 1 5 10 8111PRTHomo sapiens 81His Leu Ser Leu Leu Thr
Thr Leu Ser Asn Arg 1 5 10 8222PRTHomo sapiens 82Phe Thr Phe Thr
Leu His Leu Glu Thr Pro Lys Pro Ser Ile Ser Ser 1 5 10 15 Ser Asn
Leu Asn Pro Arg 20 8316PRTHomo sapiens 83Thr Glu Leu Arg Pro Gly
Glu Thr Leu Asn Val Asn Phe Leu Leu Arg 1 5 10 15 849PRTHomo
sapiens 84Leu Pro Thr Ala Val Val Pro Leu Arg 1 5 858PRTHomo
sapiens 85Ala Pro Leu Thr Lys Pro Leu Lys 1 5 8624PRTHomo sapiens
86Ala Asp Ser Gln Ala Gln Leu Leu Leu Ser Thr Val Val Gly Val Phe 1
5 10 15 Thr Ala Pro Gly Leu His Leu Lys 20 878PRTHomo sapiens 87Glu
Leu Pro Glu His Thr Val Lys 1 5 886PRTHomo sapiens 88Ala His Tyr
Asp Leu Arg 1 5 8913PRTHomo sapiens 89Ala Glu Ala Gln Ala Gln Tyr
Ser Ala Ala Val Ala Lys 1 5 10 907PRTHomo sapiens 90Ala Tyr Ser Asp
Leu Ser Arg 1 5 9116PRTHomo sapiens 91Asp Ala Leu Ser Ser Val Gln
Glu Ser Gln Val Ala Gln Gln Ala Arg 1 5 10 15 9210PRTHomo sapiens
92Ala Asn Arg Pro Phe Leu Val Phe Ile Arg 1 5 10 9311PRTHomo
sapiens 93Ala Leu Glu Gln Asp Leu Pro Val Asn Ile Lys 1 5 10
9414PRTHomo sapiens 94Asp Phe His Ile Asn Leu Phe Gln Val Leu Pro
Trp Leu Lys 1 5 10 9514PRTHomo sapiens 95Ala Gly Leu Leu Arg Pro
Asp Tyr Ala Leu Leu Gly His Arg 1 5 10 9619PRTHomo sapiens 96Glu
Lys Pro Ala Gly Gly Ile Pro Val Leu Gly Ser Leu Val Asn Thr 1 5 10
15 Val Leu Lys 979PRTHomo sapiens 97Ile Thr Gly Phe Leu Lys Pro Gly
Lys 1 5 987PRTHomo sapiens 98Ser Leu Leu Gln Pro Asn Lys 1 5
999PRTHomo sapiens 99Ser Pro Glu Leu Gln Ala Glu Ala Lys 1 5
10010PRTHomo sapiens 100Thr Tyr Leu His Thr Tyr Glu Ser Glu Ile 1 5
10 10112PRTHomo sapiens 101Asp Ser Pro Ser Val Trp Ala Ala Val Pro
Gly Lys 1 5 10 1028PRTHomo sapiens 102His Tyr Ile Asn Leu Ile Thr
Arg 1 5 10315PRTHomo sapiens 103Ile Pro Gly Ile Phe Glu Leu Gly Ile
Ser Ser Gln Ser Asp Arg 1 5 10 15 1049PRTHomo sapiens 104Ile Gln
Thr His Ser Thr Thr Tyr Arg 1 5 10519PRTHomo sapiens 105Gln Leu Gly
Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 1 5 10 15 His
Pro Phe 10622PRTHomo sapiens 106Phe Pro Leu Gly Ser Tyr Thr Ile Gln
Asn Ile Val Ala Gly Ser Thr 1 5 10 15 Tyr Leu Phe Ser Thr Lys 20
10713PRTHomo sapiens 107Lys Leu Val Ile Phe Asp Thr Met Leu Glu Ile
Lys Lys 1 5 10 10830PRTHomo sapiens 108Lys Phe Ile Glu Asp Asn Ile
Glu Tyr Ile Thr Ile Ile Ala Phe Ala 1 5 10 15 Gln Tyr Val Gln Glu
Ala Thr Phe Glu Glu Met Glu Lys Leu 20 25 30 10918PRTHomo sapiens
109Lys Ile Ala Pro Gln Leu Ser Thr Glu Glu Leu Val Ser Leu Gly Glu
1 5 10 15 Lys Met 11025PRTHomo sapiens 110Lys Leu Lys His Glu Leu
Thr Asp Glu Glu Leu Gln Ser Leu Phe Thr 1 5 10 15 Asn Phe Ala Asn
Val Val Asp Lys Cys 20 25 11111PRTHomo sapiens 111Lys Leu Pro Asn
Asn Val Leu Gln Glu Lys Ile 1 5 10 11219PRTHomo sapiens 112Lys Ser
Asp Val Gly Phe Leu Pro Pro Phe Pro Thr Leu Asp Pro Glu 1 5 10 15
Glu Lys Cys 11310PRTHomo sapiens 113Lys Val Met Asn His Ile Cys Ser
Lys Gln 1 5 10 11415PRTHomo sapiens 114Arg Glu Ser Leu Leu Asn His
Phe Leu Tyr Glu Val Ala Arg Arg 1 5 10 15 11510PRTHomo sapiens
115Arg Leu Cys Phe Phe Tyr Asn Lys Lys Ser 1 5 10 11621PRTHomo
sapiens 116Lys Ala Val Leu Asp Val Phe Glu Glu Gly Thr Glu Ala Ser
Ala Ala 1 5 10 15 Thr Ala Val Lys Ile 20 11710PRTHomo sapiens
117Lys Glu Gln Leu Ser Leu Leu Asp Arg Phe 1 5 10 11816PRTHomo
sapiens 118Lys Glu Gln Leu Ser Leu Leu Asp Arg Phe Thr Glu Asp Ala
Lys Arg 1 5 10 15 11917PRTHomo sapiens 119Lys Glu Gln Leu Ser Leu
Leu Asp Arg Phe Thr Glu Asp Ala Lys Arg 1 5 10 15 Leu 12025PRTHomo
sapiens 120Lys Ile Thr Asp Leu Ile Lys Asp Leu Asp Ser Gln Thr Met
Met Val 1 5 10 15 Leu Val Asn Tyr Ile Phe Phe Lys Ala 20 25
12113PRTHomo sapiens 121Lys Ile Thr Leu Leu Ser Ala Leu Val Glu Thr
Arg Thr 1 5 10 12221PRTHomo sapiens 122Lys Arg Leu Tyr Gly Ser Glu
Ala Phe Ala Thr Asp Phe Gln Asp Ser 1 5 10 15 Ala Ala Ala Lys Lys
20 12311PRTHomo sapiens 123Arg Glu Ile Gly Glu Leu Tyr Leu Pro Lys
Phe 1 5 10 12416PRTHomo sapiens 124Arg Cys Glu Gly Pro Ile Pro Asp
Val Thr Phe Glu Leu Leu Arg Glu 1 5 10 15 1257PRTHomo sapiens
125Arg Phe Ala Leu Val Arg Glu 1 5 12610PRTHomo sapiens 126Lys Ser
Pro Pro Gly Val Cys Ser Arg Asp 1 5 10 12721PRTHomo sapiens 127Arg
Asp Ser Phe His Leu Asp Glu Gln Phe Thr Val Pro Val Glu Met 1 5 10
15 Met Gln Ala Arg Thr 20 1289PRTHomo sapiens 128Lys Cys Asn Leu
Leu Ala Glu Lys Gln 1 5 12916PRTHomo sapiens 129Lys Glu His Ala Val
Glu Gly Asp Cys Asp Phe Gln Leu Leu Lys Leu 1 5 10 15 13044PRTHomo
sapiens 130Lys His Thr Leu Asn Gln Ile Asp Glu Val Lys Val Trp Pro
Gln Gln 1 5 10 15 Pro Ser Gly Glu Leu Phe Glu Ile Glu Ile Asp Thr
Leu Glu Thr Thr 20 25 30 Cys His Val Leu Asp Pro Thr Pro Val Ala
Arg Cys 35 40 13115PRTHomo sapiens 131Lys Met Val Ser Gly Phe Ile
Pro Leu Lys Pro Thr Val Lys Met 1 5 10 15 13219PRTHomo sapiens
132Arg Ala Phe Gln Pro Phe Phe Val Glu Leu Thr Met Pro Tyr Ser Val
1 5 10 15 Ile Arg Gly 13315PRTHomo sapiens 133Arg Asn Gln Gly Asn
Thr Trp Leu Thr Ala Phe Val Leu Lys Thr 1 5 10 15 13414PRTHomo
sapiens 134Lys Ile Asp Arg Phe Met Gln Ala Val Thr Gly Trp Lys Thr
1 5 10 13510PRTHomo sapiens 135Lys Leu Asp Thr Glu Asp Lys Leu Arg
Ala 1 5 10 13627PRTHomo sapiens 136Lys Thr Gly Cys Ser Leu Met Gly
Ala Ser Val Asp Ser Thr Leu Ala 1 5 10 15 Phe Asn Thr Tyr Val His
Phe Gln Gly Lys Met 20 25 13716PRTHomo sapiens 137Arg Ala Ala Met
Val Gly Met Leu Ala Asn Phe Leu Gly Phe Arg Ile 1 5 10 15
13823PRTHomo sapiens 138Lys Asn Asp Asn Asp Asn Ile Phe Leu Ser Pro
Leu Ser Ile Ser Thr 1 5 10 15 Ala Phe Ala Met Thr Lys Leu 20
13924PRTHomo sapiens 139Lys Ser Lys Leu Pro Gly Ile Val Ala Glu Gly
Arg Asp Asp Leu Tyr 1 5 10 15 Val Ser Asp Ala Phe His Lys Ala 20
14014PRTHomo sapiens 140Arg Glu Val Pro Leu Asn Thr Ile Ile Phe Met
Gly Arg Val 1 5 10 14136PRTHomo sapiens 141Arg Phe Ala Thr Thr Phe
Tyr Gln His Leu Ala Asp Ser Lys Asn Asp 1 5 10 15 Asn Asp Asn Ile
Phe Leu Ser Pro Leu Ser Ile Ser Thr Ala Phe Ala 20 25 30 Met Thr
Lys Leu 35 14227PRTHomo sapiens 142Arg Ile Thr Asp Val Ile Pro Ser
Glu Ala Ile Asn Glu Leu Thr Val 1 5 10 15 Leu Val Leu Val Asn Thr
Ile Tyr Phe Lys Gly 20 25 1439PRTHomo sapiens 143Arg Arg Val Trp
Glu Leu Ser Lys Ala 1 5
14430PRTHomo sapiens 144Arg Val Ala Glu Gly Thr Gln Val Leu Glu Leu
Pro Phe Lys Gly Asp 1 5 10 15 Asp Ile Thr Met Val Leu Ile Leu Pro
Lys Pro Glu Lys Ser 20 25 30 14523PRTHomo sapiens 145Lys Ala Gly
Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu 1 5 10 15 Gly
Thr Gln Pro Ala Thr Gln 20 14622PRTHomo sapiens 146Lys Glu Pro Cys
Val Glu Ser Leu Val Ser Gln Tyr Phe Gln Thr Val 1 5 10 15 Thr Asp
Tyr Gly Lys Asp 20 14712PRTHomo sapiens 147Lys Ala Leu Val Gln Gln
Met Glu Gln Leu Arg Gln 1 5 10 14819PRTHomo sapiens 148Lys Leu Gly
Pro His Ala Gly Asp Val Glu Gly His Leu Ser Phe Leu 1 5 10 15 Glu
Lys Asp 14916PRTHomo sapiens 149Lys Ser Glu Leu Thr Gln Gln Leu Asn
Ala Leu Phe Gln Asp Lys Leu 1 5 10 15 15020PRTHomo sapiens 150Lys
Ser Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu 1 5 10
15 Phe Arg Arg Arg 20 15114PRTHomo sapiens 151Lys Val Lys Ile Asp
Gln Thr Val Glu Glu Leu Arg Arg Ser 1 5 10 15211PRTHomo sapiens
152Lys Val Asn Ser Phe Phe Ser Thr Phe Lys Glu 1 5 10 15318PRTHomo
sapiens 153Lys Ala Thr Phe Gln Thr Pro Asp Phe Ile Val Pro Leu Thr
Asp Leu 1 5 10 15 Arg Ile 15417PRTHomo sapiens 154Lys Ala Val Ser
Met Pro Ser Phe Ser Ile Leu Gly Ser Asp Val Arg 1 5 10 15 Val
15513PRTHomo sapiens 155Lys Glu Gln His Leu Phe Leu Pro Phe Ser Tyr
Lys Asn 1 5 10 15613PRTHomo sapiens 156Lys Lys Ile Ile Ser Asp Tyr
His Gln Gln Phe Arg Tyr 1 5 10 15720PRTHomo sapiens 157Lys Gln Val
Phe Leu Tyr Pro Glu Lys Asp Glu Pro Thr Tyr Ile Leu 1 5 10 15 Asn
Ile Lys Arg 20 15812PRTHomo sapiens 158Lys Ser Pro Ala Phe Thr Asp
Leu His Leu Arg Tyr 1 5 10 15920PRTHomo sapiens 159Lys Thr Ile Leu
Gly Thr Met Pro Ala Phe Glu Val Ser Leu Gln Ala 1 5 10 15 Leu Gln
Lys Ala 20 16014PRTHomo sapiens 160Lys Val Leu Ala Asp Lys Phe Ile
Ile Pro Gly Leu Lys Leu 1 5 10 16132PRTHomo sapiens 161Lys Tyr Ser
Gln Pro Glu Asp Ser Leu Ile Pro Phe Phe Glu Ile Thr 1 5 10 15 Val
Pro Glu Ser Gln Leu Thr Val Ser Gln Phe Thr Leu Pro Lys Ser 20 25
30 16213PRTHomo sapiens 162Arg Asp Leu Lys Val Glu Asp Ile Pro Leu
Ala Arg Ile 1 5 10 16318PRTHomo sapiens 163Arg Gly Ile Ile Ser Ala
Leu Leu Val Pro Pro Glu Thr Glu Glu Ala 1 5 10 15 Lys Gln
16421PRTHomo sapiens 164Arg Ile Leu Gly Glu Glu Leu Gly Phe Ala Ser
Leu His Asp Leu Gln 1 5 10 15 Leu Leu Gly Lys Leu 20 16526PRTHomo
sapiens 165Arg Leu Glu Leu Glu Leu Arg Pro Thr Gly Glu Ile Glu Gln
Tyr Ser 1 5 10 15 Val Ser Ala Thr Tyr Glu Leu Gln Arg Glu 20 25
16617PRTHomo sapiens 166Arg Asn Ile Gln Glu Tyr Leu Ser Ile Leu Thr
Asp Pro Asp Gly Lys 1 5 10 15 Gly 16734PRTHomo sapiens 167Arg Thr
Phe Gln Ile Pro Gly Tyr Thr Val Pro Val Val Asn Val Glu 1 5 10 15
Val Ser Pro Phe Thr Ile Glu Met Ser Ala Phe Gly Tyr Val Phe Pro 20
25 30 Lys Ala 16822PRTHomo sapiens 168Arg Thr Ile Asp Gln Met Leu
Asn Ser Glu Leu Gln Trp Pro Val Pro 1 5 10 15 Asp Ile Tyr Leu Arg
Asp 20 16913PRTHomo sapiens 169Lys Met Arg Glu Trp Phe Ser Glu Thr
Phe Gln Lys Val 1 5 10 17025PRTHomo sapiens 170Lys Ser Thr Ala Ala
Met Ser Thr Tyr Thr Gly Ile Phe Thr Asp Gln 1 5 10 15 Val Leu Ser
Val Leu Lys Gly Glu Glu 20 25 17113PRTHomo sapiens 171Arg Gly Trp
Val Thr Asp Gly Phe Ser Ser Leu Lys Asp 1 5 10 17217PRTHomo sapiens
172Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg
1 5 10 15 Ala 17316PRTHomo sapiens 173Arg Leu Lys Ser Trp Phe Glu
Pro Leu Val Glu Asp Met Gln Arg Gln 1 5 10 15 17425PRTHomo sapiens
174Arg Trp Val Gln Thr Leu Ser Glu Gln Val Gln Glu Glu Leu Leu Ser
1 5 10 15 Ser Gln Val Thr Gln Glu Leu Arg Ala 20 25 17513PRTHomo
sapiens 175Lys Leu Cys Gly Gly Gly Arg Trp Glu Leu Met Arg Ile 1 5
10 1768PRTHomo sapiens 176Lys Leu Pro Gly Leu Leu Lys Arg 1 5
17711PRTHomo sapiens 177Lys Glu His Ser Ser Leu Ala Phe Trp Lys Thr
1 5 10 17819PRTHomo sapiens 178Arg Thr Cys Pro Lys Pro Asp Asp Leu
Pro Phe Ser Thr Val Val Pro 1 5 10 15 Leu Lys Thr 17916PRTHomo
sapiens 179Arg Val Cys Pro Phe Ala Gly Ile Leu Glu Asn Gly Ala Val
Arg Tyr 1 5 10 15 18014PRTHomo sapiens 180Lys Leu Phe Ala Ala Phe
Phe Leu Glu Met Ala Gln Leu His 1 5 10 18112PRTHomo sapiens 181Lys
Ser His Leu Ile Ile Ala Gln Val Ala Lys Asn 1 5 10 18214PRTHomo
sapiens 182Lys Asn Ala Ile Trp Ile Asp Cys Gly Ile His Ala Arg Glu
1 5 10 18317PRTHomo sapiens 183Arg Glu Ala Leu Ile Gln Phe Leu Glu
Gln Val His Gln Gly Ile Lys 1 5 10 15 Gly 18417PRTHomo sapiens
184Arg Leu Leu Asn Ile Gln Thr Tyr Cys Ala Gly Pro Ala Tyr Leu Lys
1 5 10 15 Gly 18520PRTHomo sapiens 185Arg Leu Cys Glu Asn Ile Ala
Gly His Leu Lys Asp Ala Gln Ile Phe 1 5 10 15 Ile Gln Lys Lys 20
18614PRTHomo sapiens 186Lys Ala Glu Thr Gly Asp Lys Val Tyr Val His
Leu Lys Asn 1 5 10 18716PRTHomo sapiens 187Lys Ala Gly Leu Gln Ala
Phe Phe Gln Val Gln Glu Cys Asn Lys Ser 1 5 10 15 18816PRTHomo
sapiens 188Lys Asp Ile Ala Ser Gly Leu Ile Gly Pro Leu Ile Ile Cys
Lys Lys 1 5 10 15 18913PRTHomo sapiens 189Lys Asp Ile Phe Thr Gly
Leu Ile Gly Pro Met Lys Ile 1 5 10 19023PRTHomo sapiens 190Lys Met
Tyr Tyr Ser Ala Val Asp Pro Thr Lys Asp Ile Phe Thr Gly 1 5 10 15
Leu Ile Gly Pro Met Lys Ile 20 19114PRTHomo sapiens 191Lys Pro Val
Trp Leu Gly Phe Leu Gly Pro Ile Ile Lys Ala 1 5 10 19235PRTHomo
sapiens 192Arg Ala Asp Asp Lys Val Tyr Pro Gly Glu Gln Tyr Thr Tyr
Met Leu 1 5 10 15 Leu Ala Thr Glu Glu Gln Ser Pro Gly Glu Gly Asp
Gly Asn Cys Val 20 25 30 Thr Arg Ile 35 19340PRTHomo sapiens 193Arg
Asp Thr Ala Asn Leu Phe Pro Gln Thr Ser Leu Thr Leu His Met 1 5 10
15 Trp Pro Asp Thr Glu Gly Thr Phe Asn Val Glu Cys Leu Thr Thr Asp
20 25 30 His Tyr Thr Gly Gly Met Lys Gln 35 40 19421PRTHomo sapiens
194Arg Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn
1 5 10 15 Pro Gln Ser Arg Ser 20 19537PRTHomo sapiens 195Arg Ile
Asp Thr Ile Asn Leu Phe Pro Ala Thr Leu Phe Asp Ala Tyr 1 5 10 15
Met Val Ala Gln Asn Pro Gly Glu Trp Met Leu Ser Cys Gln Asn Leu 20
25 30 Asn His Leu Lys Ala 35 19625PRTHomo sapiens 196Arg Lys Ala
Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln Leu His 1 5 10 15 Ala
Asp Val Gly Asp Lys Val Lys Ile 20 25 19719PRTHomo sapiens 197Arg
Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile 1 5 10
15 Ile Lys Ala 19810PRTHomo sapiens 198Arg Phe Trp Thr Ser Phe Phe
Pro Lys Val 1 5 10 19919PRTHomo sapiens 199Lys Leu Phe Asp Ser Asp
Pro Ile Thr Val Thr Val Pro Val Glu Val 1 5 10 15 Ser Arg Lys
20014PRTHomo sapiens 200Arg Ala Ser Ser Ile Ile Asp Glu Leu Phe Gln
Asp Arg Phe 1 5 10 20116PRTHomo sapiens 201Lys Trp Ile Val Thr Ala
Ala His Cys Val Glu Thr Gly Val Lys Ile 1 5 10 15 20215PRTHomo
sapiens 202Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu Asp Arg
Gly 1 5 10 15 20313PRTHomo sapiens 203Lys Glu Thr Tyr Asp Phe Asp
Ile Ala Val Leu Arg Leu 1 5 10 20419PRTHomo sapiens 204Lys Val Arg
Gln Leu Glu Met Glu Ile Gly Gln Leu Asn Val His Tyr 1 5 10 15 Leu
Arg Asn 2059PRTHomo sapiens 205Arg Pro Ala Phe Ser Ala Ile Arg Arg
1 5 20624PRTHomo sapiens 206Lys Val Val Thr Phe Cys Asp Tyr Ala Tyr
Asn Thr Phe Gln Val Thr 1 5 10 15 Thr Gly Gly Met Val Leu Lys Leu
20 20711PRTHomo sapiens 207Lys Phe Gln Ser Val Phe Thr Val Thr Arg
Gln 1 5 10 20820PRTHomo sapiens 208Lys Thr Leu Asp Glu Phe Thr Ile
Ile Gln Asn Leu Gln Pro Gln Tyr 1 5 10 15 Gln Phe Arg Asp 20
20919PRTHomo sapiens 209Arg Met Asp Val Phe Ser Gln Asn Met Phe Cys
Ala Gly His Pro Ser 1 5 10 15 Leu Lys Gln 21014PRTHomo sapiens
210Arg Trp Ile Leu Thr Ala Ala His Thr Leu Tyr Pro Lys Glu 1 5 10
21123PRTHomo sapiens 211Lys Phe Tyr Ala Ala Gly Leu Val Ser Trp Gly
Pro Gln Cys Gly Thr 1 5 10 15 Tyr Gly Leu Tyr Thr Arg Val 20
21211PRTHomo sapiens 212Lys Gly Phe Gln Val Val Val Thr Leu Arg Arg
1 5 10 21319PRTHomo sapiens 213Arg Gly Ala Leu Ile Ser Asp Gln Trp
Val Leu Thr Ala Ala His Cys 1 5 10 15 Phe Arg Asp 21417PRTHomo
sapiens 214Arg Pro Ile Cys Leu Pro Cys Thr Met Glu Ala Asn Leu Ala
Leu Arg 1 5 10 15 Arg 21526PRTHomo sapiens 215Arg Tyr Tyr Gly Gly
Gly Tyr Gly Ser Thr Gln Ala Thr Phe Met Val 1 5 10 15 Phe Gln Ala
Leu Ala Gln Tyr Gln Lys Asp 20 25 21613PRTHomo sapiens 216Lys Gly
Leu Cys Val Ala Thr Pro Val Gln Leu Arg Val 1 5 10 21721PRTHomo
sapiens 217Lys Met Arg Pro Ser Thr Asp Thr Ile Thr Val Met Val Glu
Asn Ser 1 5 10 15 His Gly Leu Arg Val 20 21823PRTHomo sapiens
218Lys Val Gly Leu Ser Gly Met Ala Ile Ala Asp Val Thr Leu Leu Ser
1 5 10 15 Gly Phe His Ala Leu Arg Ala 20 21917PRTHomo sapiens
219Lys Val Leu Ser Leu Ala Gln Glu Gln Val Gly Gly Ser Pro Glu Lys
1 5 10 15 Leu 22015PRTHomo sapiens 220Arg Glu Met Ser Gly Ser Pro
Ala Ser Gly Ile Pro Val Lys Val 1 5 10 15 22120PRTHomo sapiens
221Arg Gly Cys Gly Glu Gln Thr Met Ile Tyr Leu Ala Pro Thr Leu Ala
1 5 10 15 Ala Ser Arg Tyr 20 22211PRTHomo sapiens 222Arg Gly Leu
Gln Asp Glu Asp Gly Tyr Arg Met 1 5 10 22313PRTHomo sapiens 223Arg
Gly Gln Ile Val Phe Met Asn Arg Glu Pro Lys Arg 1 5 10 22429PRTHomo
sapiens 224Arg Lys Lys Glu Val Tyr Met Pro Ser Ser Ile Phe Gln Asp
Asp Phe 1 5 10 15 Val Ile Pro Asp Ile Ser Glu Pro Gly Thr Trp Lys
Ile 20 25 2258PRTHomo sapiens 225Arg Leu Pro Met Ser Val Arg Arg 1
5 22620PRTHomo sapiens 226Arg Leu Thr Val Ala Ala Pro Pro Ser Gly
Gly Pro Gly Phe Leu Ser 1 5 10 15 Ile Glu Arg Pro 20 2277PRTHomo
sapiens 227Arg Asn Phe Leu Val Arg Ala 1 5 22834PRTHomo sapiens
228Arg Asn Gly Glu Ser Val Lys Leu His Leu Glu Thr Asp Ser Leu Ala
1 5 10 15 Leu Val Ala Leu Gly Ala Leu Asp Thr Ala Leu Tyr Ala Ala
Gly Ser 20 25 30 Lys Ser 22911PRTHomo sapiens 229Arg Gln Gly Ser
Phe Gln Gly Gly Phe Arg Ser 1 5 10 23025PRTHomo sapiens 230Arg Thr
Leu Glu Ile Pro Gly Asn Ser Asp Pro Asn Met Ile Pro Asp 1 5 10 15
Gly Asp Phe Asn Ser Tyr Val Arg Val 20 25 23128PRTHomo sapiens
231Arg Val Thr Ala Ser Asp Pro Leu Asp Thr Leu Gly Ser Glu Gly Ala
1 5 10 15 Leu Ser Pro Gly Gly Val Ala Ser Leu Leu Arg Leu 20 25
23218PRTHomo sapiens 232Arg Tyr Leu Asp Lys Thr Glu Gln Trp Ser Thr
Leu Pro Pro Glu Thr 1 5 10 15 Lys Asp 23332PRTHomo sapiens 233Lys
Ala Asp Asn Phe Leu Leu Glu Asn Thr Leu Pro Ala Gln Ser Thr 1 5 10
15 Phe Thr Leu Ala Ile Ser Ala Tyr Ala Leu Ser Leu Gly Asp Lys Thr
20 25 30 23418PRTHomo sapiens 234Lys Ala Leu Val Glu Gly Val Asp
Gln Leu Phe Thr Asp Tyr Gln Ile 1 5 10 15 Lys Asp 23522PRTHomo
sapiens 235Lys Asp Gly His Val Ile Leu Gln Leu Asn Ser Ile Pro Ser
Ser Asp 1 5 10 15 Phe Leu Cys Val Arg Phe 20 23616PRTHomo sapiens
236Lys Asp Val Phe Leu Glu Met Asn Ile Pro Tyr Ser Val Val Arg Gly
1 5 10 15 23715PRTHomo sapiens 237Lys Glu Phe Pro Tyr Arg Ile Pro
Leu Asp Leu Val Pro Lys Thr 1 5 10 15 23814PRTHomo sapiens 238Lys
Phe Gln Asn Ser Ala Ile Leu Thr Ile Gln Pro Lys Gln 1 5 10
23919PRTHomo sapiens 239Lys Val Phe Lys Asp Val Phe Leu Glu Met Asn
Ile Pro Tyr Ser Val 1 5 10 15 Val Arg Gly 2409PRTHomo sapiens
240Arg Val Phe Gln Phe Leu Glu Lys Ser 1 5 24112PRTHomo sapiens
241Lys Asp Leu His Leu Ser Asp Val Phe Leu Lys Ala 1 5 10
24221PRTHomo sapiens 242Arg Thr Glu Cys Ile Lys Pro Val Val Gln Glu
Val Leu Thr Ile Thr 1 5 10 15 Pro Phe Gln Arg Leu 20 24311PRTHomo
sapiens 243Lys Ser Ser Gly Trp His Phe Val Val Lys Phe 1 5 10
24410PRTHomo sapiens 244Arg Ile Leu Pro Leu Thr Val Cys Lys Met 1 5
10 24515PRTHomo sapiens 245Arg Ala Leu Asp Gln Tyr Leu Met Glu Phe
Asn Ala Cys Arg Cys 1 5 10 15 24619PRTHomo sapiens 246Lys Tyr Gly
Phe Cys Glu Ala Ala Asp Gln Phe His Val Leu Asp Glu 1 5 10 15 Val
Arg Arg 24715PRTHomo sapiens 247Arg Ala Ile Glu Asp Tyr Ile Asn Glu
Phe Ser Val Arg Lys Cys 1 5 10 15 24831PRTHomo sapiens 248Arg Thr
Ala Gly Tyr Gly Ile Asn Ile Leu Gly Met Asp Pro Leu Ser 1 5 10 15
Thr Pro Phe Asp Asn Glu Phe Tyr Asn Gly Leu Cys Asn Arg Asp 20 25
30 24912PRTHomo sapiens 249Lys Ala Leu Phe Val Ser Glu Glu Glu Lys
Lys Leu 1 5 10 25010PRTHomo sapiens 250Lys Cys Leu Val Asn Leu Ile
Glu Lys Val 1 5 10 25118PRTHomo sapiens 251Lys Glu Ala Gly Ile Pro
Glu Phe Tyr Asp Tyr Asp Val Ala Leu Ile 1 5 10 15 Lys Leu
25216PRTHomo sapiens 252Lys Val Ser Glu Ala Asp Ser Ser Asn Ala Asp
Trp Val Thr Lys Gln 1 5 10 15 25320PRTHomo sapiens 253Lys Tyr Gly
Gln Thr Ile Arg
Pro Ile Cys Leu Pro Cys Thr Glu Gly 1 5 10 15 Thr Thr Arg Ala 20
25420PRTHomo sapiens 254Arg Asp Leu Glu Ile Glu Val Val Leu Phe His
Pro Asn Tyr Asn Ile 1 5 10 15 Asn Gly Lys Lys 20 25519PRTHomo
sapiens 255Arg Phe Leu Cys Thr Gly Gly Val Ser Pro Tyr Ala Asp Pro
Asn Thr 1 5 10 15 Cys Arg Gly 25613PRTHomo sapiens 256Lys Asp Gly
Trp Ser Ala Gln Pro Thr Cys Ile Lys Ser 1 5 10 25714PRTHomo sapiens
257Lys Glu Gly Trp Ile His Thr Val Cys Ile Asn Gly Arg Trp 1 5 10
25820PRTHomo sapiens 258Lys Thr Asp Cys Leu Ser Leu Pro Ser Phe Glu
Asn Ala Ile Pro Met 1 5 10 15 Gly Glu Lys Lys 20 25920PRTHomo
sapiens 259Arg Asp Thr Ser Cys Val Asn Pro Pro Thr Val Gln Asn Ala
Tyr Ile 1 5 10 15 Val Ser Arg Gln 20 26013PRTHomo sapiens 260Lys
Cys Thr Ser Thr Gly Trp Ile Pro Ala Pro Arg Cys 1 5 10 26110PRTHomo
sapiens 261Lys Ile Ile Tyr Lys Glu Asn Glu Arg Phe 1 5 10
26221PRTHomo sapiens 262Lys Ile Val Ser Ser Ala Met Glu Pro Asp Arg
Glu Tyr His Phe Gly 1 5 10 15 Gln Ala Val Arg Phe 20 26314PRTHomo
sapiens 263Arg Cys Thr Leu Lys Pro Cys Asp Tyr Pro Asp Ile Lys His
1 5 10 26413PRTHomo sapiens 264Arg Lys Gly Glu Trp Val Ala Leu Asn
Pro Leu Arg Lys 1 5 10 26514PRTHomo sapiens 265Arg Lys Gly Glu Trp
Val Ala Leu Asn Pro Leu Arg Lys Cys 1 5 10 26612PRTHomo sapiens
266Arg Arg Pro Tyr Phe Pro Val Ala Val Gly Lys Tyr 1 5 10
26713PRTHomo sapiens 267Arg Glu Ile Met Glu Asn Tyr Asn Ile Ala Leu
Arg Trp 1 5 10 26827PRTHomo sapiens 268Lys Asp Ala Ser Gly Ile Thr
Cys Gly Gly Ile Tyr Ile Gly Gly Cys 1 5 10 15 Trp Ile Leu Thr Ala
Ala His Cys Leu Arg Ala 20 25 26916PRTHomo sapiens 269Lys Val Ala
Asn Tyr Phe Asp Trp Ile Ser Tyr His Val Gly Arg Pro 1 5 10 15
27024PRTHomo sapiens 270Arg Ile Ile Phe His Glu Asn Tyr Asn Ala Gly
Thr Tyr Gln Asn Asp 1 5 10 15 Ile Ala Leu Ile Glu Met Lys Lys 20
27118PRTHomo sapiens 271Arg Tyr Gln Ile Trp Thr Thr Val Val Asp Trp
Ile His Pro Asp Leu 1 5 10 15 Lys Arg 2728PRTHomo sapiens 272Lys
Ile Ser Asn Leu Leu Lys Phe 1 5 27318PRTHomo sapiens 273Arg Trp Ser
Ala Gly Leu Thr Ser Ser Gln Val Asp Leu Tyr Ile Pro 1 5 10 15 Lys
Val 27416PRTHomo sapiens 274Lys Tyr Glu Val Gln Gly Glu Val Phe Thr
Lys Pro Gln Leu Trp Pro 1 5 10 15 27513PRTHomo sapiens 275Arg His
Val Leu Ala Ala Trp Ala Leu Gly Ala Lys Ala 1 5 10 27616PRTHomo
sapiens 276Arg Ala Gly Leu Arg Tyr Val Cys Leu Ala Glu Pro Ala Glu
Arg Arg 1 5 10 15 27719PRTHomo sapiens 277Arg Phe Thr Gln Leu Cys
Val Lys Gly Gly Gly Gly Gly Gly Asn Gly 1 5 10 15 Ile Arg Asp
27819PRTHomo sapiens 278Arg Val Gln Leu Gly Pro Tyr Gln Pro Gly Arg
Pro Ala Ala Cys Asp 1 5 10 15 Leu Arg Glu 27924PRTHomo sapiens
279Arg Gly Gly Leu Gly Ser Leu Phe Tyr Leu Thr Leu Asp Val Leu Glu
1 5 10 15 Thr Asp Cys His Val Leu Arg Lys 20 28023PRTHomo sapiens
280Arg Glu Leu Leu Ser Gln Gly Ala Thr Leu Ser Gly Trp Tyr His Leu
1 5 10 15 Cys Leu Pro Glu Gly Arg Ala 20 28116PRTHomo sapiens
281Lys Lys Thr Thr Asp Met Ile Leu Asn Glu Ile Lys Gln Gly Lys Phe
1 5 10 15 28227PRTHomo sapiens 282Lys Asn Trp Arg Asp Pro Asp Gln
Thr Asp Gly Leu Gly Leu Ser Tyr 1 5 10 15 Leu Ser Ser His Ile Ala
Asn Val Glu Arg Val 20 25 28320PRTHomo sapiens 283Lys Thr Pro Ser
Ala Ala Tyr Leu Trp Val Gly Thr Gly Ala Ser Glu 1 5 10 15 Ala Glu
Lys Thr 20 28429PRTHomo sapiens 284Arg Val Glu Lys Phe Asp Leu Val
Pro Val Pro Thr Asn Leu Tyr Gly 1 5 10 15 Asp Phe Phe Thr Gly Asp
Ala Tyr Val Ile Leu Lys Thr 20 25 28530PRTHomo sapiens 285Arg Val
Pro Phe Asp Ala Ala Thr Leu His Thr Ser Thr Ala Met Ala 1 5 10 15
Ala Gln His Gly Met Asp Asp Asp Gly Thr Gly Gln Lys Gln 20 25 30
2868PRTHomo sapiens 286Lys Phe Tyr Thr Phe Leu Lys Asn 1 5
28714PRTHomo sapiens 287Lys Gly Asp Lys Val Trp Val Tyr Pro Pro Glu
Lys Lys Glu 1 5 10 28823PRTHomo sapiens 288Lys Leu Leu Gln Asp Glu
Phe Pro Gly Ile Pro Ser Pro Leu Asp Ala 1 5 10 15 Ala Val Glu Cys
His Arg Gly 20 28918PRTHomo sapiens 289Lys Ser Gly Ala Gln Ala Thr
Trp Thr Glu Leu Pro Trp Pro His Glu 1 5 10 15 Lys Val 29027PRTHomo
sapiens 290Lys Ser Gly Ala Gln Ala Thr Trp Thr Glu Leu Pro Trp Pro
His Glu 1 5 10 15 Lys Val Asp Gly Ala Leu Cys Met Glu Lys Ser 20 25
29111PRTHomo sapiens 291Lys Val Asp Gly Ala Leu Cys Met Glu Lys Ser
1 5 10 29211PRTHomo sapiens 292Arg Asp Tyr Phe Met Pro Cys Pro Gly
Arg Gly 1 5 10 29314PRTHomo sapiens 293Arg Glu Trp Phe Trp Asp Leu
Ala Thr Gly Thr Met Lys Glu 1 5 10 29412PRTHomo sapiens 294Arg Gln
Gly His Asn Ser Val Phe Leu Ile Lys Gly 1 5 10 29532PRTHomo sapiens
295Lys His Gln Gly Thr Ile Thr Val Asn Glu Glu Gly Thr Gln Ala Thr
1 5 10 15 Thr Val Thr Thr Val Gly Phe Met Pro Leu Ser Thr Gln Val
Arg Phe 20 25 30 29613PRTHomo sapiens 296Lys Tyr Glu Ile Thr Thr
Ile His Asn Leu Phe Arg Lys 1 5 10 2979PRTHomo sapiens 297Arg Leu
Asn Ile Leu Asn Ala Lys Phe 1 5 2989PRTHomo sapiens 298Arg Asn Phe
Gly Tyr Thr Leu Arg Ser 1 5 29921PRTHomo sapiens 299Arg Val Gln Leu
Ser Pro Asp Leu Leu Ala Thr Leu Pro Glu Pro Ala 1 5 10 15 Ser Pro
Gly Arg Gln 20 30011PRTHomo sapiens 300Arg Asp Gly Tyr Leu Phe Gln
Leu Leu Arg Ile 1 5 10 3018PRTHomo sapiens 301Lys Phe Leu Asn Trp
Ile Lys Ala 1 5 30215PRTHomo sapiens 302Lys Leu Lys Pro Val Asp Gly
His Cys Ala Leu Glu Ser Lys Tyr 1 5 10 15 30312PRTHomo sapiens
303Lys Arg Pro Gly Val Tyr Thr Gln Val Thr Lys Phe 1 5 10
30423PRTHomo sapiens 304Lys Ala Gly Ala Asp Thr His Gly Arg Leu Leu
Gln Gly Asn Ile Cys 1 5 10 15 Asn Asp Ala Val Thr Lys Ala 20
30516PRTHomo sapiens 305Lys Lys Ile Ile Glu Lys Met Ala Thr Phe Glu
Ile Asp Glu Lys Arg 1 5 10 15 30624PRTHomo sapiens 306Arg Ser Phe
Glu Gly Leu Gly Gln Leu Glu Val Leu Thr Leu Asp His 1 5 10 15 Asn
Gln Leu Gln Glu Val Lys Ala 20 30711PRTHomo sapiens 307Lys Glu Leu
Ala Ala Gln Thr Ile Lys Lys Ser 1 5 10 30821PRTHomo sapiens 308Lys
Gly Ser Leu Val Gln Ala Ser Glu Ala Asn Leu Gln Ala Ala Gln 1 5 10
15 Asp Phe Val Arg Gly 20 30922PRTHomo sapiens 309Lys Gln Leu Val
His His Phe Glu Ile Asp Val Asp Ile Phe Glu Pro 1 5 10 15 Gln Gly
Ile Ser Lys Leu 20 31015PRTHomo sapiens 310Lys Gln Tyr Tyr Glu Gly
Ser Glu Ile Val Val Ala Gly Arg Ile 1 5 10 15 31133PRTHomo sapiens
311Arg Glu Val Ala Phe Asp Leu Glu Ile Pro Lys Thr Ala Phe Ile Ser
1 5 10 15 Asp Phe Ala Val Thr Ala Asp Gly Asn Ala Phe Ile Gly Asp
Ile Lys 20 25 30 Asp 31230PRTHomo sapiens 312Arg Gly Met Ala Asp
Gln Asp Gly Leu Lys Pro Thr Ile Asp Lys Pro 1 5 10 15 Ser Glu Asp
Ser Pro Pro Leu Glu Met Leu Gly Pro Arg Arg 20 25 30 31341PRTHomo
sapiens 313Lys Phe Asp Pro Ala Lys Leu Asp Gln Ile Glu Ser Val Ile
Thr Ala 1 5 10 15 Thr Ser Ala Asn Thr Gln Leu Val Leu Glu Thr Leu
Ala Gln Met Asp 20 25 30 Asp Leu Gln Asp Phe Leu Ser Lys Asp 35 40
31414PRTHomo sapiens 314Lys Lys Phe Tyr Asn Gln Val Ser Thr Pro Leu
Leu Arg Asn 1 5 10 31518PRTHomo sapiens 315Lys Asn Ile Leu Phe Val
Ile Asp Val Ser Gly Ser Met Trp Gly Val 1 5 10 15 Lys Met
31610PRTHomo sapiens 316Arg Lys Leu Gly Ser Tyr Glu His Arg Ile 1 5
10 31713PRTHomo sapiens 317Arg Leu Ser Asn Glu Asn His Gly Ile Ala
Gln Arg Ile 1 5 10 31811PRTHomo sapiens 318Arg Met Ala Thr Thr Met
Ile Gln Ser Lys Val 1 5 10 31930PRTHomo sapiens 319Arg Ser Ile Leu
Gln Met Ser Leu Asp His His Ile Val Thr Pro Leu 1 5 10 15 Thr Ser
Leu Val Ile Glu Asn Glu Ala Gly Asp Glu Arg Met 20 25 30
32012PRTHomo sapiens 320Arg Thr Glu Val Asn Val Leu Pro Gly Ala Lys
Val 1 5 10 32110PRTHomo sapiens 321Lys Asn Val Val Phe Val Ile Asp
Lys Ser 1 5 10 32215PRTHomo sapiens 322Lys Trp Lys Glu Thr Leu Phe
Ser Val Met Pro Gly Leu Lys Met 1 5 10 15 32311PRTHomo sapiens
323Lys Tyr Ile Phe His Asn Phe Met Glu Arg Leu 1 5 10 32411PRTHomo
sapiens 324Arg Phe Ala His Thr Val Val Thr Ser Arg Val 1 5 10
32512PRTHomo sapiens 325Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys
Ser 1 5 10 32646PRTHomo sapiens 326Arg Ile His Glu Asp Ser Asp Ser
Ala Leu Gln Leu Gln Asp Phe Tyr 1 5 10 15 Gln Glu Val Ala Asn Pro
Leu Leu Thr Ala Val Thr Phe Glu Tyr Pro 20 25 30 Ser Asn Ala Val
Glu Glu Val Thr Gln Asn Asn Phe Arg Leu 35 40 45 32713PRTHomo
sapiens 327Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln 1 5
10 32813PRTHomo sapiens 328Arg Asn Val His Ser Ala Gly Ala Ala Gly
Ser Arg Met 1 5 10 32912PRTHomo sapiens 329Arg Asn Val His Ser Gly
Ser Thr Phe Phe Lys Tyr 1 5 10 33012PRTHomo sapiens 330Arg Arg Leu
Gly Val Tyr Glu Leu Leu Leu Lys Val 1 5 10 33110PRTHomo sapiens
331Lys Lys Leu Glu Leu His Leu Pro Lys Phe 1 5 10 33215PRTHomo
sapiens 332Arg Glu Ile Glu Glu Val Leu Thr Pro Glu Met Leu Met Arg
Trp 1 5 10 15 33315PRTHomo sapiens 333Lys Ala Ala Thr Gly Glu Cys
Thr Ala Thr Val Gly Lys Arg Ser 1 5 10 15 33420PRTHomo sapiens
334Lys Leu Gly Gln Ser Leu Asp Cys Asn Ala Glu Val Tyr Val Val Pro
1 5 10 15 Trp Glu Lys Lys 20 33517PRTHomo sapiens 335Lys Tyr Asn
Ser Gln Asn Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg 1 5 10 15 Ile
33611PRTHomo sapiens 336Arg Gln Val Val Ala Gly Leu Asn Phe Arg Ile
1 5 10 33712PRTHomo sapiens 337Lys Asp Leu Leu Leu Pro Gln Pro Asp
Leu Arg Tyr 1 5 10 33815PRTHomo sapiens 338Arg Leu His Leu Glu Gly
Asn Lys Leu Gln Val Leu Gly Lys Asp 1 5 10 15 33920PRTHomo sapiens
339Arg Thr Leu Asp Leu Gly Glu Asn Gln Leu Glu Thr Leu Pro Pro Asp
1 5 10 15 Leu Leu Arg Gly 20 34021PRTHomo sapiens 340Lys Gly Leu
Gln Tyr Ala Ala Gln Glu Gly Leu Leu Ala Leu Gln Ser 1 5 10 15 Glu
Leu Leu Arg Ile 20 34113PRTHomo sapiens 341Lys Leu Ala Glu Gly Phe
Pro Leu Pro Leu Leu Lys Arg 1 5 10 34216PRTHomo sapiens 342Lys Ser
Leu Glu Tyr Leu Asp Leu Ser Phe Asn Gln Ile Ala Arg Leu 1 5 10 15
34313PRTHomo sapiens 343Arg Leu Lys Glu Asp Ala Val Ser Ala Ala Phe
Lys Gly 1 5 10 34421PRTHomo sapiens 344Arg Ile Val Phe Glu Asn Pro
Asp Pro Ser Asp Gly Phe Val Leu Ile 1 5 10 15 Pro Asp Leu Lys Trp
20 3457PRTHomo sapiens 345Arg Val Tyr Phe Phe Lys Gly 1 5
3468PRTHomo sapiens 346Lys Trp Phe Asp Tyr Leu Arg Glu 1 5
34720PRTHomo sapiens 347Arg Leu Thr Val Gly Ala Ala Gln Val Pro Ala
Gln Leu Leu Val Gly 1 5 10 15 Ala Leu Arg Val 20 34818PRTHomo
sapiens 348Arg Val Ser Phe Ser Ser Pro Leu Val Ala Ile Ser Gly Val
Ala Leu 1 5 10 15 Arg Ser 34919PRTHomo sapiens 349Lys Gly Ile Val
Ala Ala Phe Tyr Ser Gly Pro Ser Leu Ser Asp Lys 1 5 10 15 Glu Lys
Leu 35016PRTHomo sapiens 350Arg Trp Tyr Val Pro Val Lys Asp Leu Leu
Gly Ile Tyr Glu Lys Leu 1 5 10 15 35114PRTHomo sapiens 351Lys Leu
Gln Ser Leu Phe Asp Ser Pro Asp Phe Ser Lys Ile 1 5 10 35219PRTHomo
sapiens 352Arg Ala Leu Tyr Tyr Asp Leu Ile Ser Ser Pro Asp Ile His
Gly Thr 1 5 10 15 Tyr Lys Glu 35320PRTHomo sapiens 353Arg Cys Leu
Leu Phe Ser Phe Leu Pro Ala Ser Ser Ile Asn Asp Met 1 5 10 15 Glu
Lys Arg Phe 20 35412PRTHomo sapiens 354Lys Phe Gln Pro Thr Leu Leu
Thr Leu Pro Arg Ile 1 5 10 35519PRTHomo sapiens 355Lys Gly Val Thr
Ser Val Ser Gln Ile Phe His Ser Pro Asp Leu Ala 1 5 10 15 Ile Arg
Asp 35618PRTHomo sapiens 356Lys Val Ile Pro Ala Cys Leu Pro Ser Pro
Asn Tyr Val Val Ala Asp 1 5 10 15 Arg Thr 35712PRTHomo sapiens
357Arg Phe Val Thr Trp Ile Glu Gly Val Met Arg Asn 1 5 10
35813PRTHomo sapiens 358Arg His Ser Ile Phe Thr Pro Glu Thr Asn Pro
Arg Ala 1 5 10 35917PRTHomo sapiens 359Lys Gly Lys Glu Glu Ser Leu
Asp Ser Asp Leu Tyr Ala Glu Leu Arg 1 5 10 15 Cys 36017PRTHomo
sapiens 360Lys Met Val Leu Leu Glu Gln Leu Phe Leu Asp His Asn Ala
Leu Arg 1 5 10 15 Gly 36124PRTHomo sapiens 361Arg Leu Val Ser Leu
Asp Ser Gly Leu Leu Asn Ser Leu Gly Ala Leu 1 5 10 15 Thr Glu Leu
Gln Phe His Arg Asn 20 36214PRTHomo sapiens 362Lys Ala Leu Leu Ala
Tyr Ala Phe Ser Leu Leu Gly Lys Gln 1 5 10 36314PRTHomo sapiens
363Lys Asp Leu Phe His Cys Val Ser Phe Thr Leu Pro Arg Ile 1 5 10
36414PRTHomo sapiens 364Lys Met Leu Gln Ile Thr Asn Thr Gly Phe Glu
Met Lys Leu 1 5 10 36516PRTHomo sapiens 365Arg Asn Glu Leu Ile Pro
Leu Ile Tyr Leu Glu Asn Pro Arg Arg Asn 1 5 10 15 36624PRTHomo
sapiens 366Arg Ser Tyr Ile Phe Ile Asp Glu Ala His Ile Thr Gln Ser
Leu Thr 1 5 10 15 Trp Leu Ser Gln Met Gln Lys Asp 20 36718PRTHomo
sapiens 367Arg Ser Asp Pro Val Thr Leu Asn Leu Leu His Gly Pro Asp
Leu Pro 1 5 10
15 Arg Ile 36811PRTHomo sapiens 368Arg Thr Leu Phe Leu Phe Gly Val
Thr Lys Tyr 1 5 10 36911PRTHomo sapiens 369Arg Ile Leu Ile Leu Pro
Ser Val Thr Arg Asn 1 5 10 37013PRTHomo sapiens 370Arg Ser Asp Pro
Val Thr Leu Asn Leu Leu Pro Lys Leu 1 5 10 3718PRTHomo sapiens
371Arg Val Leu Gln Leu Glu Lys Gln 1 5 37221PRTHomo sapiens 372Arg
Val Val Ala Gln Gly Val Gly Ile Pro Glu Asp Ser Ile Phe Thr 1 5 10
15 Met Ala Asp Arg Gly 20 37328PRTHomo sapiens 373Arg Leu Thr Glu
Arg Glu Trp Ala Asp Glu Trp Lys His Leu Asp His 1 5 10 15 Ala Leu
Asn Cys Ile Met Glu Met Val Glu Lys Thr 20 25 37421PRTHomo sapiens
374Arg Ala Leu Cys Gly Gly Asp Gly Ala Ala Ala Leu Arg Glu Pro Gly
1 5 10 15 Ala Gly Leu Arg Leu 20 37524PRTHomo sapiens 375Lys Ala
Leu Met Asp Leu Leu Ala Gly Lys Gly Ser Gln Gly Ser Gln 1 5 10 15
Ala Pro Gln Ala Leu Asp Arg Thr 20 37623PRTHomo sapiens 376Lys Met
Gly Asp His Leu Ala Leu Glu Asp Tyr Leu Thr Thr Asp Leu 1 5 10 15
Val Glu Thr Trp Leu Arg Asn 20 37717PRTHomo sapiens 377Lys Ser Pro
Gln Glu Leu Leu Cys Gly Ala Ser Leu Ile Ser Asp Arg 1 5 10 15 Trp
37821PRTHomo sapiens 378Arg Leu Ala Val Thr Thr His Gly Leu Pro Cys
Leu Ala Trp Ala Ser 1 5 10 15 Ala Gln Ala Lys Ala 20 37921PRTHomo
sapiens 379Arg Ser Glu Gly Ser Ser Val Asn Leu Ser Pro Pro Leu Glu
Gln Cys 1 5 10 15 Val Pro Asp Arg Gly 20 38011PRTHomo sapiens
380Arg Ser Gly Ile Glu Cys Gln Leu Trp Arg Ser 1 5 10 38115PRTHomo
sapiens 381Arg Thr Ala Thr Ser Glu Tyr Gln Thr Phe Phe Asn Pro Arg
Thr 1 5 10 15 38219PRTHomo sapiens 382Arg Val Thr Gly Trp Gly Asn
Leu Lys Glu Thr Trp Thr Ala Asn Val 1 5 10 15 Gly Lys Gly
3839PRTHomo sapiens 383Arg Ile His Leu Met Ala Gly Arg Val 1 5
3849PRTHomo sapiens 384Arg Pro Ala His Pro Ala Leu Arg Leu 1 5
3858PRTHomo sapiens 385Lys Ile Ser Asn Ile Ile Lys Gln 1 5
38614PRTHomo sapiens 386Lys Met Lys Tyr Trp Gly Val Ala Ser Phe Leu
Gln Lys Gly 1 5 10 38712PRTHomo sapiens 387Arg Phe Ser Gly Thr Trp
Tyr Ala Met Ala Lys Lys 1 5 10 38820PRTHomo sapiens 388Arg Leu Leu
Asn Leu Asp Gly Thr Cys Ala Asp Ser Tyr Ser Phe Val 1 5 10 15 Phe
Ser Arg Asp 20 38927PRTHomo sapiens 389Arg Leu Leu Asn Asn Trp Asp
Val Cys Ala Asp Met Val Gly Thr Phe 1 5 10 15 Thr Asp Thr Glu Asp
Pro Ala Lys Phe Lys Met 20 25 39028PRTHomo sapiens 390Arg Leu Phe
Leu Gly Ala Leu Pro Gly Glu Asp Ser Ser Thr Ser Phe 1 5 10 15 Cys
Leu Asn Gly Leu Trp Ala Gln Gly Gln Arg Leu 20 25 39111PRTHomo
sapiens 391Lys Asp Asp Trp Phe Met Leu Gly Leu Arg Asp 1 5 10
39225PRTHomo sapiens 392Arg Ser Cys Asp Val Glu Ser Asn Pro Gly Ile
Phe Leu Pro Pro Gly 1 5 10 15 Thr Gln Ala Glu Phe Asn Leu Arg Gly
20 25 39327PRTHomo sapiens 393Arg Thr Trp Asp Pro Glu Gly Val Ile
Phe Tyr Gly Asp Thr Asn Pro 1 5 10 15 Lys Asp Asp Trp Phe Met Leu
Gly Leu Arg Asp 20 25 39426PRTHomo sapiens 394Arg Lys Phe Cys Arg
Asp Ile Gln Asp Pro Thr Gln Leu Ala Glu Met 1 5 10 15 Ile Phe Asn
Leu Leu Leu Glu Glu Lys Arg 20 25 39516PRTHomo sapiens 395Arg Asn
Glu Leu Ile Arg Gln Glu Lys Leu Glu Gln Leu Ala Arg Arg 1 5 10 15
3968PRTHomo sapiens 396Arg Lys Asn Leu Ser Glu Arg Trp 1 5
39712PRTHomo sapiens 397Arg Lys Trp Tyr Asn Leu Met Ile Gln Asn Lys
Asp 1 5 10 39816PRTHomo sapiens 398Lys Ser Arg Leu Asp Thr Leu Ala
Gln Glu Val Ala Leu Leu Lys Glu 1 5 10 15 39916PRTHomo sapiens
399Lys Arg Leu Asp Val Asn Ala Ala Gly Ile Trp Glu Pro Lys Lys Gly
1 5 10 15 4009PRTHomo sapiens 400Arg Ser Ile Leu Phe Leu Gly Lys
Val 1 5 40128PRTHomo sapiens 401Arg Glu Leu Ile Ser Asp Leu Glu His
Arg Leu Gln Gly Ser Val Met 1 5 10 15 Glu Leu Leu Gln Gly Val Asp
Gly Val Ile Lys Arg 20 25 40227PRTHomo sapiens 402Lys Glu Leu Ser
Ser Phe Ile Asp Lys Gly Gln Glu Leu Cys Ala Asp 1 5 10 15 Tyr Ser
Glu Asn Thr Phe Thr Glu Tyr Lys Lys 20 25 40328PRTHomo sapiens
403Lys Glu Leu Ser Ser Phe Ile Asp Lys Gly Gln Glu Leu Cys Ala Asp
1 5 10 15 Tyr Ser Glu Asn Thr Phe Thr Glu Tyr Lys Lys Lys 20 25
40424PRTHomo sapiens 404Lys Glu Val Val Ser Leu Thr Glu Ala Cys Cys
Ala Glu Gly Ala Asp 1 5 10 15 Pro Asp Cys Tyr Asp Thr Arg Thr 20
40540PRTHomo sapiens 405Lys Thr Ala Met Asp Val Phe Val Cys Thr Tyr
Phe Met Pro Ala Ala 1 5 10 15 Gln Leu Pro Glu Leu Pro Asp Val Glu
Leu Pro Thr Asn Lys Asp Val 20 25 30 Cys Asp Pro Gly Asn Thr Lys
Val 35 40 40613PRTHomo sapiens 406Arg Arg Thr His Leu Pro Glu Val
Phe Leu Ser Lys Val 1 5 10 40713PRTHomo sapiens 407Arg Val Cys Ser
Gln Tyr Ala Ala Tyr Gly Glu Lys Lys 1 5 10 40820PRTHomo sapiens
408Lys Leu Ile Arg Asp Val Trp Gly Ile Glu Gly Pro Ile Asp Ala Ala
1 5 10 15 Phe Thr Arg Ile 20 40917PRTHomo sapiens 409Arg Asp Val
Trp Gly Ile Glu Gly Pro Ile Asp Ala Ala Phe Thr Arg 1 5 10 15 Ile
4109PRTHomo sapiens 410Arg Glu Arg Val Tyr Phe Phe Lys Gly 1 5
41114PRTHomo sapiens 411Arg Phe Glu Asp Gly Val Leu Asp Pro Asp Tyr
Pro Arg Asn 1 5 10 41216PRTHomo sapiens 412Arg Ile Tyr Ile Ser Gly
Met Ala Pro Arg Pro Ser Leu Ala Lys Lys 1 5 10 15 4138PRTHomo
sapiens 413Lys Thr Arg Phe Leu Leu Arg Thr 1 5 41423PRTHomo sapiens
414Lys His Glu Leu Thr Asp Glu Glu Leu Gln Ser Leu Phe Thr Asn Phe
1 5 10 15 Ala Asn Val Val Asp Lys Cys 20 41523PRTHomo sapiens
415Arg Asn Pro Phe Val Phe Ala Pro Thr Leu Leu Thr Val Ala Val His
1 5 10 15 Phe Glu Glu Val Ala Lys Ser 20 41612PRTHomo sapiens
416Lys Ala Asp Leu Ser Gly Ile Thr Gly Ala Arg Asn 1 5 10
41717PRTHomo sapiens 417Lys Met Glu Glu Val Glu Ala Met Leu Leu Pro
Glu Thr Leu Lys Arg 1 5 10 15 Trp 41816PRTHomo sapiens 418Lys Trp
Glu Met Pro Phe Asp Pro Gln Asp Thr His Gln Ser Arg Phe 1 5 10 15
41920PRTHomo sapiens 419Arg Leu Tyr Gly Ser Glu Ala Phe Ala Thr Asp
Phe Gln Asp Ser Ala 1 5 10 15 Ala Ala Lys Lys 20 42014PRTHomo
sapiens 420Lys His Gln Phe Leu Leu Thr Gly Asp Thr Gln Gly Arg Tyr
1 5 10 42118PRTHomo sapiens 421Lys Asn Gly Val Ala Gln Glu Pro Val
His Leu Asp Ser Pro Ala Ile 1 5 10 15 Lys His 42222PRTHomo sapiens
422Lys Ser Leu Pro Ala Pro Trp Leu Ser Met Ala Pro Val Ser Trp Ile
1 5 10 15 Thr Pro Gly Leu Lys Thr 20 42320PRTHomo sapiens 423Lys
Val Thr Leu Thr Cys Val Ala Pro Leu Ser Gly Val Asp Phe Gln 1 5 10
15 Leu Arg Arg Gly 20 42411PRTHomo sapiens 424Arg Cys Leu Ala Pro
Leu Glu Gly Ala Arg Phe 1 5 10 4259PRTHomo sapiens 425Arg Gly Val
Thr Phe Leu Leu Arg Arg 1 5 42639PRTHomo sapiens 426Arg Leu His Asp
Asn Gln Asn Gly Trp Ser Gly Asp Ser Ala Pro Val 1 5 10 15 Glu Leu
Ile Leu Ser Asp Glu Thr Leu Pro Ala Pro Glu Phe Ser Pro 20 25 30
Glu Pro Glu Ser Gly Arg Ala 35 42724PRTHomo sapiens 427Arg Thr Pro
Gly Ala Ala Ala Asn Leu Glu Leu Ile Phe Val Gly Pro 1 5 10 15 Gln
His Ala Gly Asn Tyr Arg Cys 20 42826PRTHomo sapiens 428Lys His Gln
Met Asp Leu Val Ala Thr Leu Ser Gln Leu Gly Leu Gln 1 5 10 15 Glu
Leu Phe Gln Ala Pro Asp Leu Arg Gly 20 25 42913PRTHomo sapiens
429Arg Leu Cys Gln Asp Leu Gly Pro Gly Ala Phe Arg Leu 1 5 10
43019PRTHomo sapiens 430Arg Trp Phe Leu Leu Glu Gln Pro Glu Ile Gln
Val Ala His Phe Pro 1 5 10 15 Phe Lys Asn 43134PRTHomo sapiens
431Lys Val Trp Pro Gln Gln Pro Ser Gly Glu Leu Phe Glu Ile Glu Ile
1 5 10 15 Asp Thr Leu Glu Thr Thr Cys His Val Leu Asp Pro Thr Pro
Val Ala 20 25 30 Arg Cys 43222PRTHomo sapiens 432Arg His Thr Phe
Met Gly Val Val Ser Leu Gly Ser Pro Ser Gly Glu 1 5 10 15 Val Ser
His Pro Arg Lys 20 43331PRTHomo sapiens 433Arg Gln Pro Asn Cys Asp
Asp Pro Glu Thr Glu Glu Ala Ala Leu Val 1 5 10 15 Ala Ile Asp Tyr
Ile Asn Gln Asn Leu Pro Trp Gly Tyr Lys His 20 25 30 43423PRTHomo
sapiens 434Arg Thr Val Val Gln Pro Ser Val Gly Ala Ala Ala Gly Pro
Val Val 1 5 10 15 Pro Pro Cys Pro Gly Arg Ile 20 43519PRTHomo
sapiens 435Lys Gln Pro Phe Val Gln Gly Leu Ala Leu Tyr Thr Pro Val
Val Leu 1 5 10 15 Pro Arg Ser 43613PRTHomo sapiens 436Lys Leu Val
Pro Phe Ala Thr Glu Leu His Glu Arg Leu 1 5 10 43713PRTHomo sapiens
437Arg Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile 1 5 10
43827PRTHomo sapiens 438Arg Ser Leu Ala Pro Tyr Ala Gln Asp Thr Gln
Glu Lys Leu Asn His 1 5 10 15 Gln Leu Glu Gly Leu Thr Phe Gln Met
Lys Lys 20 25 43911PRTHomo sapiens 439Lys Phe Pro Glu Val Asp Val
Leu Thr Lys Tyr 1 5 10 44011PRTHomo sapiens 440Lys His Ile Asn Ile
Asp Gln Phe Val Arg Lys 1 5 10 44117PRTHomo sapiens 441Lys Leu Leu
Ser Gly Gly Asn Thr Leu His Leu Val Ser Thr Thr Lys 1 5 10 15 Thr
44221PRTHomo sapiens 442Lys Gln Val Phe Leu Tyr Pro Glu Lys Asp Glu
Pro Thr Tyr Ile Leu 1 5 10 15 Asn Ile Lys Arg Gly 20 44310PRTHomo
sapiens 443Lys Ser Leu His Met Tyr Ala Asn Arg Leu 1 5 10
44419PRTHomo sapiens 444Lys Ser Val Ser Asp Gly Ile Ala Ala Leu Asp
Leu Asn Ala Val Ala 1 5 10 15 Asn Lys Ile 44530PRTHomo sapiens
445Lys Ser Val Ser Leu Pro Ser Leu Asp Pro Ala Ser Ala Lys Ile Glu
1 5 10 15 Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr Leu Pro Lys Glu
20 25 30 44613PRTHomo sapiens 446Lys Thr Glu Val Ile Pro Pro Leu
Ile Glu Asn Arg Gln 1 5 10 44712PRTHomo sapiens 447Lys Val Leu Val
Asp His Phe Gly Tyr Thr Lys Asp 1 5 10 44826PRTHomo sapiens 448Arg
Thr Ser Ser Phe Ala Leu Asn Leu Pro Thr Leu Pro Glu Val Lys 1 5 10
15 Phe Pro Glu Val Asp Val Leu Thr Lys Tyr 20 25 44920PRTHomo
sapiens 449Arg Gly Trp Val Thr Asp Gly Phe Ser Ser Leu Lys Asp Tyr
Trp Ser 1 5 10 15 Thr Val Lys Asp 20 45017PRTHomo sapiens 450Arg
Gly Glu Val Gln Ala Met Leu Gly Gln Ser Thr Glu Glu Leu Arg 1 5 10
15 Val 45111PRTHomo sapiens 451Arg Leu Ala Val Tyr Gln Ala Gly Ala
Arg Glu 1 5 10 45211PRTHomo sapiens 452Arg Leu Gly Pro Leu Val Glu
Gln Gly Arg Val 1 5 10 45312PRTHomo sapiens 453Lys Leu Thr Leu Thr
Pro Trp Val Gly Leu Arg Lys 1 5 10 45417PRTHomo sapiens 454Lys Phe
Ile Cys Pro Leu Thr Gly Leu Trp Pro Ile Asn Thr Leu Lys 1 5 10 15
Cys 45522PRTHomo sapiens 455Lys Thr Phe Tyr Glu Pro Gly Glu Glu Ile
Thr Tyr Ser Cys Lys Pro 1 5 10 15 Gly Tyr Val Ser Arg Gly 20
45627PRTHomo sapiens 456Lys Met Val Val Ser Met Thr Leu Gly Leu His
Pro Trp Ile Ala Asn 1 5 10 15 Ile Asp Asp Thr Gln Tyr Leu Ala Ala
Lys Arg 20 25 45719PRTHomo sapiens 457Lys Val Phe Gln Tyr Ile Asp
Leu His Gln Asp Glu Phe Val Gln Thr 1 5 10 15 Leu Lys Glu
45819PRTHomo sapiens 458Arg Thr Ser Ile Tyr Pro Phe Leu Asp Phe Met
Pro Ser Pro Gln Val 1 5 10 15 Val Arg Trp 45917PRTHomo sapiens
459Arg Glu Leu Met Leu Gln Leu Ser Glu Phe Leu Cys Glu Glu Phe Arg
1 5 10 15 Asn 46024PRTHomo sapiens 460Lys Ala Glu Glu Glu His Leu
Gly Ile Leu Gly Pro Gln Leu His Ala 1 5 10 15 Asp Val Gly Asp Lys
Val Lys Ile 20 46114PRTHomo sapiens 461Lys Ala Leu Tyr Leu Gln Tyr
Thr Asp Glu Thr Phe Arg Thr 1 5 10 46228PRTHomo sapiens 462Lys Asp
Val Asp Lys Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu 1 5 10 15
Asn Glu Ser Leu Leu Leu Glu Asp Asn Ile Arg Met 20 25 46322PRTHomo
sapiens 463Lys His Tyr Tyr Ile Gly Ile Ile Glu Thr Thr Trp Asp Tyr
Ala Ser 1 5 10 15 Asp His Gly Glu Lys Lys 20 46413PRTHomo sapiens
464Arg Glu Tyr Thr Asp Ala Ser Phe Thr Asn Arg Lys Glu 1 5 10
46525PRTHomo sapiens 465Arg His Tyr Tyr Ile Ala Ala Glu Glu Ile Ile
Trp Asn Tyr Ala Pro 1 5 10 15 Ser Gly Ile Asp Ile Phe Thr Lys Glu
20 25 46612PRTHomo sapiens 466Arg Ile Tyr His Ser His Ile Asp Ala
Pro Lys Asp 1 5 10 46730PRTHomo sapiens 467Arg Gln Lys Asp Val Asp
Lys Glu Phe Tyr Leu Phe Pro Thr Val Phe 1 5 10 15 Asp Glu Asn Glu
Ser Leu Leu Leu Glu Asp Asn Ile Arg Met 20 25 30 46819PRTHomo
sapiens 468Arg Thr Tyr Tyr Ile Ala Ala Val Glu Val Glu Trp Asp Tyr
Ser Pro 1 5 10 15 Gln Arg Glu 46911PRTHomo sapiens 469Arg Ser Ala
Leu Val Leu Gln Tyr Leu Arg Val 1 5 10 47014PRTHomo sapiens 470Lys
Glu Phe Asn Pro Leu Val Ile Val Gly Leu Ser Lys Asp 1 5 10
47117PRTHomo sapiens 471Arg Asn Pro Asp Asn Asp Ile Arg Pro Trp Cys
Phe Val Leu Asn Arg 1 5 10 15 Asp 47211PRTHomo sapiens 472Arg Val
Val Gly Gly Leu Val Ala Leu Arg Gly 1 5 10 47325PRTHomo sapiens
473Lys Asn Ser Leu Leu Gly Met Glu Gly Ala Asn Ser Ile Phe Ser Gly
1 5 10 15 Phe Leu Leu Phe Pro Asp Met Glu Ala 20 25 47416PRTHomo
sapiens 474Lys Val Pro Gly Leu Tyr Tyr Phe Thr Tyr His Ala Ser Ser
Arg Gly 1 5 10 15
47515PRTHomo sapiens 475Arg Gln Thr His Gln Pro Pro Ala Pro Asn Ser
Leu Ile Arg Phe 1 5 10 15 47616PRTHomo sapiens 476Arg Leu Pro Val
Ala Asn Pro Gln Ala Cys Glu Asn Trp Leu Arg Gly 1 5 10 15
47718PRTHomo sapiens 477Lys Asn Gln Gly Ile Leu Glu Phe Tyr Gly Asp
Asp Ile Ala Leu Leu 1 5 10 15 Lys Leu 47816PRTHomo sapiens 478Lys
Arg Asn Asp Tyr Leu Asp Ile Tyr Ala Ile Gly Val Gly Lys Leu 1 5 10
15 47933PRTHomo sapiens 479Arg Gln Pro Tyr Ser Tyr Asp Phe Pro Glu
Asp Val Ala Pro Ala Leu 1 5 10 15 Gly Thr Ser Phe Ser His Met Leu
Gly Ala Thr Asn Pro Thr Gln Lys 20 25 30 Thr 48012PRTHomo sapiens
480Arg Ile His Trp Glu Ser Ala Ser Leu Leu Arg Ser 1 5 10
4819PRTHomo sapiens 481Lys Phe Ala Cys Tyr Tyr Pro Arg Val 1 5
48228PRTHomo sapiens 482Lys Leu His Leu Glu Thr Asp Ser Leu Ala Leu
Val Ala Leu Gly Ala 1 5 10 15 Leu Asp Thr Ala Leu Tyr Ala Ala Gly
Ser Lys Ser 20 25 48314PRTHomo sapiens 483Lys Leu Val Asn Gly Gln
Ser His Ile Ser Leu Ser Lys Ala 1 5 10 48411PRTHomo sapiens 484Lys
Ser Cys Gly Leu His Gln Leu Leu Arg Gly 1 5 10 48511PRTHomo sapiens
485Lys Tyr Val Leu Pro Asn Phe Glu Val Lys Ile 1 5 10 48621PRTHomo
sapiens 486Arg Ala Leu Glu Ile Leu Gln Glu Glu Asp Leu Ile Asp Glu
Asp Asp 1 5 10 15 Ile Pro Val Arg Ser 20 48733PRTHomo sapiens
487Arg Glu Cys Val Gly Phe Glu Ala Val Gln Glu Val Pro Val Gly Leu
1 5 10 15 Val Gln Pro Ala Ser Ala Thr Leu Tyr Asp Tyr Tyr Asn Pro
Glu Arg 20 25 30 Arg 48815PRTHomo sapiens 488Arg Glu Glu Leu Val
Tyr Glu Leu Asn Pro Leu Asp His Arg Gly 1 5 10 15 48927PRTHomo
sapiens 489Arg Ser Thr Gln Asp Thr Val Ile Ala Leu Asp Ala Leu Ser
Ala Tyr 1 5 10 15 Trp Ile Ala Ser His Thr Thr Glu Glu Arg Gly 20 25
49012PRTHomo sapiens 490Arg Val Gly Asp Thr Leu Asn Leu Asn Leu Arg
Ala 1 5 10 49111PRTHomo sapiens 491Arg Val His Tyr Thr Val Cys Ile
Trp Arg Asn 1 5 10 49212PRTHomo sapiens 492Lys Lys Tyr Val Leu Pro
Asn Phe Glu Val Lys Ile 1 5 10 49326PRTHomo sapiens 493Lys Val Asp
Phe Thr Leu Ser Ser Glu Arg Asp Phe Ala Leu Leu Ser 1 5 10 15 Leu
Gln Val Pro Leu Lys Asp Ala Lys Ser 20 25 49418PRTHomo sapiens
494Arg Ser Tyr Phe Pro Glu Ser Trp Leu Trp Glu Val His Leu Val Pro
1 5 10 15 Arg Arg 49528PRTHomo sapiens 495Arg Tyr Gly Gly Gly Phe
Tyr Ser Thr Gln Asp Thr Ile Asn Ala Ile 1 5 10 15 Glu Gly Leu Thr
Glu Tyr Ser Leu Leu Val Lys Gln 20 25 49612PRTHomo sapiens 496Arg
His Thr Ser Leu Gly Pro Leu Glu Ala Lys Arg 1 5 10 49735PRTHomo
sapiens 497Lys Cys Gln His Glu Met Asp Gln Tyr Trp Gly Ile Gly Ser
Leu Ala 1 5 10 15 Ser Gly Ile Asn Leu Phe Thr Asn Ser Phe Glu Gly
Pro Val Leu Asp 20 25 30 His Arg Tyr 35 49810PRTHomo sapiens 498Lys
Ser Gly Phe Ser Phe Gly Phe Lys Ile 1 5 10 49914PRTHomo sapiens
499Arg Asp Thr Met Val Glu Asp Leu Val Val Leu Val Arg Gly 1 5 10
50024PRTHomo sapiens 500Lys Ala Asn Phe Asp Ala Gln Gln Phe Ala Gly
Thr Trp Leu Leu Val 1 5 10 15 Ala Val Gly Ser Ala Cys Arg Phe 20
50123PRTHomo sapiens 501Arg Ala Glu Ala Thr Thr Leu His Val Ala Pro
Gln Gly Thr Ala Met 1 5 10 15 Ala Val Ser Thr Phe Arg Lys 20
50215PRTHomo sapiens 502Arg Asp Val Val Leu Thr Thr Thr Phe Val Asp
Asp Ile Lys Ala 1 5 10 15 50315PRTHomo sapiens 503Arg Arg Pro Trp
Asn Val Ala Ser Leu Ile Tyr Glu Thr Lys Gly 1 5 10 15 50410PRTHomo
sapiens 504Lys Ile Ser Val Ile Arg Pro Ser Lys Gly 1 5 10
50511PRTHomo sapiens 505Lys Val Ala Ser Tyr Gly Val Lys Pro Arg Tyr
1 5 10 50616PRTHomo sapiens 506Arg Asp Phe His Ile Asn Leu Phe Gln
Val Leu Pro Trp Leu Lys Glu 1 5 10 15 5079PRTHomo sapiens 507Arg
Asp Leu Leu Tyr Ile Gly Lys Asp 1 5 50813PRTHomo sapiens 508Arg Leu
Glu Asp Ser Val Thr Tyr His Cys Ser Arg Gly 1 5 10 50913PRTHomo
sapiens 509Arg Leu Pro Pro Thr Thr Thr Cys Gln Gln Gln Lys Glu 1 5
10 51011PRTHomo sapiens 510Lys Cys Leu His Pro Cys Val Ile Ser Arg
Glu 1 5 10 51111PRTHomo sapiens 511Lys Ile Asp Val His Leu Val Pro
Asp Arg Lys 1 5 10 51216PRTHomo sapiens 512Lys Ser Ile Asp Val Ala
Cys His Pro Gly Tyr Ala Leu Pro Lys Ala 1 5 10 15 51325PRTHomo
sapiens 513Lys Val Ser Val Leu Cys Gln Glu Asn Tyr Leu Ile Gln Glu
Gly Glu 1 5 10 15 Glu Ile Thr Cys Lys Asp Gly Arg Trp 20 25
51415PRTHomo sapiens 514Lys Trp Ser Ser Pro Pro Gln Cys Glu Gly Leu
Pro Cys Lys Ser 1 5 10 15 51512PRTHomo sapiens 515Arg Trp Gln Ser
Ile Pro Leu Cys Val Glu Lys Ile 1 5 10 51619PRTHomo sapiens 516Arg
Tyr Gln Ile Trp Thr Thr Val Val Asp Trp Ile His Pro Asp Leu 1 5 10
15 Lys Arg Ile 51732PRTHomo sapiens 517Lys Ala Val Leu Gln Leu Asn
Glu Glu Gly Val Asp Thr Ala Gly Ser 1 5 10 15 Thr Gly Val Thr Leu
Asn Leu Thr Ser Lys Pro Ile Ile Leu Arg Phe 20 25 30 51817PRTHomo
sapiens 518Arg Gly Leu Ala Ser Ala Asn Val Asp Phe Ala Phe Ser Leu
Tyr Lys 1 5 10 15 His 51922PRTHomo sapiens 519Lys Thr Phe Pro Gly
Phe Phe Ser Pro Met Leu Gly Glu Phe Val Ser 1 5 10 15 Glu Thr Glu
Ser Arg Gly 20 52026PRTHomo sapiens 520Lys Phe Asp Leu Val Pro Val
Pro Thr Asn Leu Tyr Gly Asp Phe Phe 1 5 10 15 Thr Gly Asp Ala Tyr
Val Ile Leu Lys Thr 20 25 52119PRTHomo sapiens 521Lys Gln Thr Gln
Val Ser Val Leu Pro Glu Gly Gly Glu Thr Pro Leu 1 5 10 15 Phe Lys
Gln 52224PRTHomo sapiens 522Arg Ala Gln Pro Val Gln Val Ala Glu Gly
Ser Glu Pro Asp Gly Phe 1 5 10 15 Trp Glu Ala Leu Gly Gly Lys Ala
20 52332PRTHomo sapiens 523Arg Ile Glu Gly Ser Asn Lys Val Pro Val
Asp Pro Ala Thr Tyr Gly 1 5 10 15 Gln Phe Tyr Gly Gly Asp Ser Tyr
Ile Ile Leu Tyr Asn Tyr Arg His 20 25 30 52414PRTHomo sapiens
524Lys Phe Leu Val Gly Pro Asp Gly Ile Pro Ile Met Arg Trp 1 5 10
52517PRTHomo sapiens 525Lys Ala Leu Pro Gln Pro Gln Asn Val Thr Ser
Leu Leu Gly Cys Thr 1 5 10 15 His 52632PRTHomo sapiens 526Lys Ser
Leu Gly Pro Asn Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr 1 5 10 15
Leu Ile His Gly Pro Asn Leu Tyr Cys Tyr Ser Asp Val Glu Lys Leu 20
25 30 52730PRTHomo sapiens 527Arg Asp Gly Trp His Ser Trp Pro Ile
Ala His Gln Trp Pro Gln Gly 1 5 10 15 Pro Ser Ala Val Asp Ala Ala
Phe Ser Trp Glu Glu Lys Leu 20 25 30 52817PRTHomo sapiens 528Arg
Gly Glu Cys Gln Ala Glu Gly Val Leu Phe Phe Gln Gly Asp Arg 1 5 10
15 Glu 52929PRTHomo sapiens 529Arg Gly Glu Cys Gln Ala Glu Gly Val
Leu Phe Phe Gln Gly Asp Arg 1 5 10 15 Glu Trp Phe Trp Asp Leu Ala
Thr Gly Thr Met Lys Glu 20 25 53029PRTHomo sapiens 530Arg Leu Glu
Lys Glu Val Gly Thr Pro His Gly Ile Ile Leu Asp Ser 1 5 10 15 Val
Asp Ala Ala Phe Ile Cys Pro Gly Ser Ser Arg Leu 20 25 5319PRTHomo
sapiens 531Arg Leu Trp Trp Leu Asp Leu Lys Ser 1 5 53215PRTHomo
sapiens 532Arg Trp Lys Asn Phe Pro Ser Pro Val Asp Ala Ala Phe Arg
Gln 1 5 10 15 53330PRTHomo sapiens 533Lys Asp Gln Val Asn Thr Phe
Asp Asn Ile Phe Ile Ala Pro Val Gly 1 5 10 15 Ile Ser Thr Ala Met
Gly Met Ile Ser Leu Gly Leu Lys Gly 20 25 30 53411PRTHomo sapiens
534Lys Ala Asn Val Phe Val Gln Leu Pro Arg Leu 1 5 10 53516PRTHomo
sapiens 535Arg Leu Glu Ala Leu Pro Asn Ser Leu Leu Ala Pro Leu Gly
Arg Leu 1 5 10 15 5369PRTHomo sapiens 536Arg Leu Phe Gln Gly Leu
Gly Lys Leu 1 5 53717PRTHomo sapiens 537Arg Asn Leu Ile Ala Ala Val
Ala Pro Gly Ala Phe Leu Gly Leu Lys 1 5 10 15 Ala 53813PRTHomo
sapiens 538Arg Thr Phe Thr Pro Gln Pro Pro Gly Leu Glu Arg Leu 1 5
10 53914PRTHomo sapiens 539Lys Val Thr Phe Gln Leu Thr Tyr Glu Glu
Val Leu Lys Arg 1 5 10 54015PRTHomo sapiens 540Lys Val Thr Phe Gln
Leu Thr Tyr Glu Glu Val Leu Lys Arg Asn 1 5 10 15 54139PRTHomo
sapiens 541Arg Gly Ile Glu Ile Leu Asn Gln Val Gln Glu Ser Leu Pro
Glu Leu 1 5 10 15 Ser Asn His Ala Ser Ile Leu Ile Met Leu Thr Asp
Gly Asp Pro Thr 20 25 30 Glu Gly Val Thr Asp Arg Ser 35
54215PRTHomo sapiens 542Arg Lys Ala Ala Ile Ser Gly Glu Asn Ala Gly
Leu Val Arg Ala 1 5 10 15 54327PRTHomo sapiens 543Lys Ala Gly Glu
Leu Glu Val Phe Asn Gly Tyr Phe Val His Phe Phe 1 5 10 15 Ala Pro
Asp Asn Leu Asp Pro Ile Pro Lys Asn 20 25 54413PRTHomo sapiens
544Lys Phe Tyr Asn Gln Val Ser Thr Pro Leu Leu Arg Asn 1 5 10
54513PRTHomo sapiens 545Lys Val Gln Phe Glu Leu His Tyr Gln Glu Val
Lys Trp 1 5 10 54617PRTHomo sapiens 546Arg Glu Thr Ala Val Asp Gly
Glu Leu Val Val Leu Tyr Asp Val Lys 1 5 10 15 Arg 5479PRTHomo
sapiens 547Arg Ile Tyr Leu Gln Pro Gly Arg Leu 1 5 54815PRTHomo
sapiens 548Arg Leu Trp Ala Tyr Leu Thr Ile Glu Gln Leu Leu Glu Lys
Arg 1 5 10 15 54914PRTHomo sapiens 549Lys Ile Thr Phe Glu Leu Val
Tyr Glu Glu Leu Leu Lys Arg 1 5 10 55018PRTHomo sapiens 550Lys Leu
Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly 1 5 10 15
Lys Leu 55129PRTHomo sapiens 551Lys Thr Gly Leu Leu Leu Leu Ser Asp
Pro Asp Lys Val Thr Ile Gly 1 5 10 15 Leu Leu Phe Trp Asp Gly Arg
Gly Glu Gly Leu Arg Leu 20 25 55230PRTHomo sapiens 552Arg Ala Ile
Ser Gly Gly Ser Ile Gln Ile Glu Asn Gly Tyr Phe Val 1 5 10 15 His
Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro Lys Asn 20 25 30
55317PRTHomo sapiens 553Arg Ala Asn Thr Val Gln Glu Ala Thr Phe Gln
Met Glu Leu Pro Lys 1 5 10 15 Lys 55435PRTHomo sapiens 554Arg Ser
Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile Asn 1 5 10 15
Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln Glu 20
25 30 Glu Arg Leu 35 55512PRTHomo sapiens 555Arg Val Gln Gly Asn
Asp His Ser Ala Thr Arg Glu 1 5 10 55615PRTHomo sapiens 556Lys Ile
Thr Phe Glu Leu Val Tyr Glu Glu Leu Leu Lys Arg Arg 1 5 10 15
55713PRTHomo sapiens 557Lys Val Thr Ile Gly Leu Leu Phe Trp Asp Gly
Arg Gly 1 5 10 55828PRTHomo sapiens 558Arg Leu Trp Ala Tyr Leu Thr
Ile Gln Gln Leu Leu Glu Gln Thr Val 1 5 10 15 Ser Ala Ser Asp Ala
Asp Gln Gln Ala Leu Arg Asn 20 25 55923PRTHomo sapiens 559Lys Leu
Phe His Thr Asn Phe Tyr Asp Thr Val Gly Thr Ile Gln Leu 1 5 10 15
Ile Asn Asp His Val Lys Lys 20 56013PRTHomo sapiens 560Lys Glu Asn
Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser 1 5 10 56119PRTHomo sapiens
561Lys Ile Tyr Pro Thr Val Asn Cys Gln Pro Leu Gly Met Ile Ser Leu
1 5 10 15 Met Lys Arg 56220PRTHomo sapiens 562Lys Lys Ile Tyr Pro
Thr Val Asn Cys Gln Pro Leu Gly Met Ile Ser 1 5 10 15 Leu Met Lys
Arg 20 56323PRTHomo sapiens 563Lys Ser Leu Trp Asn Gly Asp Thr Gly
Glu Cys Thr Asp Asn Ala Tyr 1 5 10 15 Ile Asp Ile Gln Leu Arg Ile
20 56411PRTHomo sapiens 564Lys Ile Leu Gly Pro Leu Ser Tyr Ser Lys
Ile 1 5 10 56531PRTHomo sapiens 565Lys Glu Tyr Gly Val Val Leu Ala
Pro Asp Gly Ser Thr Val Ala Val 1 5 10 15 Glu Pro Leu Leu Ala Gly
Leu Glu Ala Gly Leu Gln Gly Arg Arg 20 25 30 56634PRTHomo sapiens
566Arg Glu Gly Lys Glu Tyr Gly Val Val Leu Ala Pro Asp Gly Ser Thr
1 5 10 15 Val Ala Val Glu Pro Leu Leu Ala Gly Leu Glu Ala Gly Leu
Gln Gly 20 25 30 Arg Arg 56727PRTHomo sapiens 567Arg Gln Asn Gly
Ala Ala Leu Thr Ser Ala Ser Ile Leu Ala Gln Gln 1 5 10 15 Val Trp
Gly Thr Leu Val Leu Leu Gln Arg Leu 20 25 56821PRTHomo sapiens
568Lys Ile Ala Gln Leu Pro Leu Thr Gly Ser Met Ser Ile Ile Phe Phe
1 5 10 15 Leu Pro Leu Lys Val 20 56932PRTHomo sapiens 569Arg Ser
Ser Thr Ser Pro Thr Thr Asn Val Leu Leu Ser Pro Leu Ser 1 5 10 15
Val Ala Thr Ala Leu Ser Ala Leu Ser Leu Gly Ala Glu Gln Arg Thr 20
25 30 57013PRTHomo sapiens 570Lys Val Ala Glu Tyr Met Asp Trp Ile
Leu Glu Lys Thr 1 5 10 57115PRTHomo sapiens 571Arg Cys Gln Phe Phe
Ser Tyr Ala Thr Gln Thr Phe His Lys Ala 1 5 10 15 57219PRTHomo
sapiens 572Arg Cys Leu Leu Phe Ser Phe Leu Pro Ala Ser Ser Ile Asn
Asp Met 1 5 10 15 Glu Lys Arg 57314PRTHomo sapiens 573Arg Leu Val
Leu Leu Asn Ala Ile Tyr Leu Ser Ala Lys Trp 1 5 10 57416PRTHomo
sapiens 574Arg Asn Ala Leu Phe Cys Leu Glu Ser Ala Trp Asn Val Ala
Lys Glu 1 5 10 15 57518PRTHomo sapiens 575Arg Ser Asn Pro Val Ile
Leu Asn Val Leu Tyr Gly Pro Asp Leu Pro 1 5 10 15 Arg Ile
57620PRTHomo sapiens 576Lys Ile Ala Ile Ile Gly Ala Gly Ile Gly Gly
Thr Ser Ala Ala Tyr 1 5 10 15 Tyr Leu Arg Gln 20 57716PRTHomo
sapiens 577Lys Trp Tyr Asn Leu Ala Ile Gly Ser Thr Cys Pro Trp Leu
Lys Lys 1 5 10 15 57813PRTHomo sapiens 578Arg Thr Val Ala Ala Cys
Asn Leu Pro Ile Val Arg Gly 1 5 10 57922PRTHomo sapiens 579Arg Ile
Val Glu Gly Ser Asp Ala Glu Ile Gly Met Ser Pro Trp Gln 1 5 10 15
Val
Met Leu Phe Arg Lys 20 58023PRTHomo sapiens 580Arg Arg Gln Glu Cys
Ser Ile Pro Val Cys Gly Gln Asp Gln Val Thr 1 5 10 15 Val Ala Met
Thr Pro Arg Ser 20 58119PRTHomo sapiens 581Arg Thr Phe Gly Ser Gly
Glu Ala Asp Cys Gly Leu Arg Pro Leu Phe 1 5 10 15 Glu Lys Lys
58225PRTHomo sapiens 582Arg Leu Leu Asn Asn Trp Asp Val Cys Ala Asp
Met Val Gly Thr Phe 1 5 10 15 Thr Asp Thr Glu Asp Pro Ala Lys Phe
20 25 58312PRTHomo sapiens 583Arg Gly Tyr Val Ile Ile Lys Pro Leu
Val Trp Val 1 5 10 58426PRTHomo sapiens 584Lys Val Val Leu Ser Ser
Gly Ser Gly Pro Gly Leu Asp Leu Pro Leu 1 5 10 15 Val Leu Gly Leu
Pro Leu Gln Leu Lys Leu 20 25 58511PRTHomo sapiens 585Lys Gly Phe
Leu Leu Leu Ala Ser Leu Arg Gln 1 5 10 58610PRTHomo sapiens 586Lys
Ala Val Leu His Ile Gly Glu Lys Gly 1 5 10 58717PRTHomo sapiens
587Lys Phe Ser Ile Ser Ala Thr Tyr Asp Leu Gly Ala Thr Leu Leu Lys
1 5 10 15 Met 58817PRTHomo sapiens 588Lys Lys Glu Leu Glu Leu Gln
Ile Gly Asn Ala Leu Phe Ile Gly Lys 1 5 10 15 His 58916PRTHomo
sapiens 589Lys Met Ser Ser Ile Asn Ala Asp Phe Ala Phe Asn Leu Tyr
Arg Arg 1 5 10 15 59014PRTHomo sapiens 590Arg Leu Thr Leu Leu Ala
Pro Leu Asn Ser Val Phe Lys Asp 1 5 10 59115PRTHomo sapiens 591Arg
Gly Ser Pro Ala Ile Asn Val Ala Val His Val Phe Arg Lys 1 5 10 15
59211PRTHomo sapiens 592Lys Met Pro Ser His Leu Met Leu Ala Arg Lys
1 5 10 59310PRTHomo sapiens 593Lys Glu Leu Pro Glu His Thr Val Lys
Leu 1 5 10 59429PRTHomo sapiens 594Lys Glu Tyr Ala Asn Gln Phe Met
Trp Glu Tyr Ser Thr Asn Tyr Gly 1 5 10 15 Gln Ala Pro Leu Ser Leu
Leu Val Ser Tyr Thr Lys Ser 20 25 59513PRTHomo sapiens 595Lys His
Leu Ser Leu Leu Thr Thr Leu Ser Asn Arg Val 1 5 10 59624PRTHomo
sapiens 596Lys His Gln Pro Gln Glu Phe Pro Thr Tyr Val Glu Pro Thr
Asn Asp 1 5 10 15 Glu Ile Cys Glu Ala Phe Arg Lys 20 59728PRTHomo
sapiens 597Lys Leu Ala Gln Lys Val Pro Thr Ala Asp Leu Glu Asp Val
Leu Pro 1 5 10 15 Leu Ala Glu Asp Ile Thr Asn Ile Leu Ser Lys Cys
20 25 59810PRTHomo sapiens 598Lys Leu Cys Asp Asn Leu Ser Thr Lys
Asn 1 5 10 5999PRTHomo sapiens 599Lys Leu Cys Met Ala Ala Leu Lys
His 1 5 60022PRTHomo sapiens 600Lys Ser Cys Glu Ser Asn Ser Pro Phe
Pro Val His Pro Gly Thr Ala 1 5 10 15 Glu Cys Cys Thr Lys Glu 20
60123PRTHomo sapiens 601Lys Ser Tyr Leu Ser Met Val Gly Ser Cys Cys
Thr Ser Ala Ser Pro 1 5 10 15 Thr Val Cys Phe Leu Lys Glu 20
60231PRTHomo sapiens 602Lys Thr Ala Met Asp Val Phe Val Cys Thr Tyr
Phe Met Pro Ala Ala 1 5 10 15 Gln Leu Pro Glu Leu Pro Asp Val Glu
Leu Pro Thr Asn Lys Asp 20 25 30 6039PRTHomo sapiens 603Lys Val Leu
Glu Pro Thr Leu Lys Ser 1 5 60417PRTHomo sapiens 604Arg Lys Phe Pro
Ser Gly Thr Phe Glu Gln Val Ser Gln Leu Val Lys 1 5 10 15 Glu
60512PRTHomo sapiens 605Arg Thr His Leu Pro Glu Val Phe Leu Ser Lys
Val 1 5 10 6069PRTHomo sapiens 606Arg Thr Ser Ala Leu Ser Ala Lys
Ser 1 5 60712PRTHomo sapiens 607Arg Gly Gln Tyr Cys Tyr Glu Leu Asp
Glu Lys Ala 1 5 10 60824PRTHomo sapiens 608Arg Met Asp Trp Leu Val
Pro Ala Thr Cys Glu Pro Ile Gln Ser Val 1 5 10 15 Phe Phe Phe Ser
Gly Asp Lys Tyr 20 6099PRTHomo sapiens 609Arg Gln Pro Gln Phe Ile
Ser Arg Asp 1 5 6109PRTHomo sapiens 610Lys His Phe Gln Asn Leu Gly
Lys Asp 1 5 61114PRTHomo sapiens 611Arg Arg His Pro Asp Leu Ser Ile
Pro Glu Leu Leu Arg Ile 1 5 10 61213PRTHomo sapiens 612Arg Thr Ile
Asn Pro Ala Val Asp His Cys Cys Lys Thr 1 5 10 61322PRTHomo sapiens
613Arg Asp Tyr Asn Leu Asn Asp Ile Leu Leu Gln Leu Gly Ile Glu Glu
1 5 10 15 Ala Phe Thr Ser Lys Ala 20 61423PRTHomo sapiens 614Arg
Gly Thr His Val Asp Leu Gly Leu Ala Ser Ala Asn Val Asp Phe 1 5 10
15 Ala Phe Ser Leu Tyr Lys Gln 20 61528PRTHomo sapiens 615Lys Gly
Phe Pro Ile Lys Glu Asp Phe Leu Glu Gln Ser Glu Gln Leu 1 5 10 15
Phe Gly Ala Lys Pro Val Ser Leu Thr Gly Lys Gln 20 25 61620PRTHomo
sapiens 616Arg Gln Leu Thr Ser Gly Pro Asn Gln Glu Gln Val Ser Pro
Leu Thr 1 5 10 15 Leu Leu Lys Leu 20 61726PRTHomo sapiens 617Arg
Ala Gln Leu Val Pro Leu Pro Pro Ser Thr Tyr Val Glu Phe Thr 1 5 10
15 Val Ser Gly Thr Asp Cys Val Ala Lys Glu 20 25 61814PRTHomo
sapiens 618Lys Asp Pro Thr Phe Ile Pro Ala Pro Ile Gln Ala Lys Thr
1 5 10 61911PRTHomo sapiens 619Arg Phe Met Gln Ala Val Thr Gly Trp
Lys Thr 1 5 10 62012PRTHomo sapiens 620Lys Ala Asn Arg Pro Phe Leu
Val Phe Ile Arg Glu 1 5 10 62117PRTHomo sapiens 621Lys Gly Asp Asp
Ile Thr Met Val Leu Ile Leu Pro Lys Pro Glu Lys 1 5 10 15 Ser
62213PRTHomo sapiens 622Arg Asp Ile Pro Met Asn Pro Met Cys Ile Tyr
Arg Ser 1 5 10 62314PRTHomo sapiens 623Lys Lys Leu Val Pro Phe Ala
Thr Glu Leu His Glu Arg Leu 1 5 10 62419PRTHomo sapiens 624Lys Ser
Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu 1 5 10 15
Phe Arg Arg 62517PRTHomo sapiens 625Lys Ala Leu Tyr Trp Val Asn Gly
Gln Val Pro Asp Gly Val Ser Lys 1 5 10 15 Val 6269PRTHomo sapiens
626Lys Phe Ile Ile Pro Gly Leu Lys Leu 1 5 62720PRTHomo sapiens
627Lys Phe Ser Val Pro Ala Gly Ile Val Ile Pro Ser Phe Gln Ala Leu
1 5 10 15 Thr Ala Arg Phe 20 62817PRTHomo sapiens 628Lys Ile Glu
Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr Leu Pro Lys 1 5 10 15 Glu
62928PRTHomo sapiens 629Lys Leu Asn Asp Leu Asn Ser Val Leu Val Met
Pro Thr Phe His Val 1 5 10 15 Pro Phe Thr Asp Leu Gln Val Pro Ser
Cys Lys Leu 20 25 63016PRTHomo sapiens 630Lys Val Glu Leu Glu Val
Pro Gln Leu Cys Ser Phe Ile Leu Lys Thr 1 5 10 15 63118PRTHomo
sapiens 631Lys Val Asn Trp Glu Glu Glu Ala Ala Ser Gly Leu Leu Thr
Ser Leu 1 5 10 15 Lys Asp 63217PRTHomo sapiens 632Arg Ala Thr Leu
Tyr Ala Leu Ser His Ala Val Asn Asn Tyr His Lys 1 5 10 15 Thr
63312PRTHomo sapiens 633Arg Thr Gly Ile Ser Pro Leu Ala Leu Ile Lys
Gly 1 5 10 63416PRTHomo sapiens 634Arg Thr Leu Gln Gly Ile Pro Gln
Met Ile Gly Glu Val Ile Arg Lys 1 5 10 15 63518PRTHomo sapiens
635Lys Asp Ala Leu Ser Ser Val Gln Glu Ser Gln Val Ala Gln Gln Ala
1 5 10 15 Arg Gly 63615PRTHomo sapiens 636Arg Asp Gly Trp Gln Trp
Phe Trp Ser Pro Ser Thr Phe Arg Gly 1 5 10 15 63718PRTHomo sapiens
637Lys Val Gln Ala Ala Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp
1 5 10 15 Asn His 6389PRTHomo sapiens 638Arg Trp Glu Leu Ala Leu
Gly Arg Phe 1 5 63924PRTHomo sapiens 639Lys Ser Asn Phe Leu Asn Cys
Tyr Val Ser Gly Phe His Pro Ser Asp 1 5 10 15 Ile Glu Val Asp Leu
Leu Lys Asn 20 64012PRTHomo sapiens 640Arg Gly Gly His Cys Val Ala
Leu Cys Thr Arg Gly 1 5 10 64122PRTHomo sapiens 641Arg Leu Val Asp
Phe Tyr Val Met Pro Val Val Asn Val Asp Gly Tyr 1 5 10 15 Asp Tyr
Ser Trp Lys Lys 20 64229PRTHomo sapiens 642Arg Tyr Thr His Gly His
Gly Ser Glu Thr Leu Tyr Leu Ala Pro Gly 1 5 10 15 Gly Gly Asp Asp
Trp Ile Tyr Asp Leu Gly Ile Lys Tyr 20 25 64318PRTHomo sapiens
643Lys Leu Ser Asn Asn Ala Leu Ser Gly Leu Pro Gln Gly Val Phe Gly
1 5 10 15 Lys Leu 64429PRTHomo sapiens 644Lys Thr Leu Asn Leu Ala
Gln Asn Leu Leu Ala Gln Leu Pro Glu Glu 1 5 10 15 Leu Phe His Pro
Leu Thr Ser Leu Gln Thr Leu Lys Leu 20 25 64511PRTHomo sapiens
645Arg Trp Leu Asn Val Gln Leu Ser Pro Arg Gln 1 5 10 64632PRTHomo
sapiens 646Lys Gly Asp Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn
Glu Ala 1 5 10 15 Asp Val His Gly Ile Tyr Phe Ser Gly Asn Thr Tyr
Leu Trp Arg Gly 20 25 30 64712PRTHomo sapiens 647Lys Met Tyr Tyr
Ser Ala Val Asp Pro Thr Lys Asp 1 5 10 64825PRTHomo sapiens 648Arg
Gly Pro Glu Glu Glu His Leu Gly Ile Leu Gly Pro Val Ile Trp 1 5 10
15 Ala Glu Val Gly Asp Thr Ile Arg Val 20 25 64939PRTHomo sapiens
649Arg Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile Pro Trp Ala Tyr
1 5 10 15 Tyr Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser Gly Leu
Ile Gly 20 25 30 Pro Leu Ile Val Cys Arg Arg 35 65013PRTHomo
sapiens 650Lys Ile Phe Phe Pro Gly Val Ser Glu Phe Gly Lys Glu 1 5
10 65123PRTHomo sapiens 651Arg Ala Ile Leu Gln Ser Gly Ser Phe Asn
Ala Pro Trp Ala Val Thr 1 5 10 15 Ser Leu Tyr Glu Ala Arg Asn 20
65219PRTHomo sapiens 652Arg Val Leu Gln Gly Val Leu Pro Ala Leu Pro
Gln Val Val Cys Asn 1 5 10 15 Tyr Arg Asp 65316PRTHomo sapiens
653Arg Ile Ser Leu Leu Leu Ile Glu Ser Trp Leu Glu Pro Val Arg Phe
1 5 10 15 65420PRTHomo sapiens 654Arg Leu His Glu Ala Phe Ser Pro
Val Ser Tyr Gln His Asp Leu Ala 1 5 10 15 Leu Leu Arg Leu 20
65520PRTHomo sapiens 655Arg Thr Thr Leu Ser Gly Ala Pro Cys Gln Pro
Trp Ala Ser Glu Ala 1 5 10 15 Thr Tyr Arg Asn 20 65629PRTHomo
sapiens 656Lys Gly Leu Phe Gln Val Val Ser Gly Gly Met Val Leu Gln
Leu Gln 1 5 10 15 Gln Gly Asp Gln Val Trp Val Glu Lys Asp Pro Lys
Lys 20 25 65712PRTHomo sapiens 657Lys Val Leu Asn Tyr Val Asp Trp
Ile Lys Lys Glu 1 5 10 65818PRTHomo sapiens 658Lys Ser Asn Ala Leu
Asp Ile Ile Phe Gln Thr Asp Leu Thr Gly Gln 1 5 10 15 Lys Lys
65921PRTHomo sapiens 659Lys Glu Gly Ala Ile His Arg Glu Glu Leu Val
Tyr Glu Leu Asn Pro 1 5 10 15 Leu Asp His Arg Gly 20 66011PRTHomo
sapiens 660Lys Ile Thr Gln Val Leu His Phe Thr Lys Asp 1 5 10
66111PRTHomo sapiens 661Lys Ser His Ala Leu Gln Leu Asn Asn Arg Gln
1 5 10 66220PRTHomo sapiens 662Arg Ala Val Gly Ser Gly Ala Thr Phe
Ser His Tyr Tyr Tyr Met Ile 1 5 10 15 Leu Ser Arg Gly 20
66316PRTHomo sapiens 663Arg Glu Pro Phe Leu Ser Cys Cys Gln Phe Ala
Glu Ser Leu Arg Lys 1 5 10 15 66419PRTHomo sapiens 664Arg Gly His
Leu Phe Leu Gln Thr Asp Gln Pro Ile Tyr Asn Pro Gly 1 5 10 15 Gln
Arg Val 66515PRTHomo sapiens 665Arg Gly Leu Glu Glu Glu Leu Gln Phe
Ser Leu Gly Ser Lys Ile 1 5 10 15 66615PRTHomo sapiens 666Arg Gly
Ser Phe Glu Phe Pro Val Gly Asp Ala Val Ser Lys Val 1 5 10 15
66719PRTHomo sapiens 667Arg Leu Leu Ala Thr Leu Cys Ser Ala Glu Val
Cys Gln Cys Ala Glu 1 5 10 15 Gly Lys Cys 66824PRTHomo sapiens
668Arg Val Gln Gln Pro Asp Cys Arg Glu Pro Phe Leu Ser Cys Cys Gln
1 5 10 15 Phe Ala Glu Ser Leu Arg Lys Lys 20 66916PRTHomo sapiens
669Arg Tyr Ile Tyr Gly Lys Pro Val Gln Gly Val Ala Tyr Val Arg Phe
1 5 10 15 67013PRTHomo sapiens 670Lys Ile Thr His Tyr Asn Tyr Leu
Ile Leu Ser Lys Gly 1 5 10 67117PRTHomo sapiens 671Arg Glu Asn Ser
Leu Tyr Leu Thr Ala Phe Thr Val Ile Gly Ile Arg 1 5 10 15 Lys
67212PRTHomo sapiens 672Arg Lys Ala Phe Asp Ile Cys Pro Leu Val Lys
Ile 1 5 10 67326PRTHomo sapiens 673Arg Val Asp Asp Gly Val Ala Ser
Phe Val Leu Asn Leu Pro Ser Gly 1 5 10 15 Val Thr Val Leu Glu Phe
Asn Val Lys Thr 20 25 67430PRTHomo sapiens 674Lys Thr Phe Ser Glu
Trp Leu Glu Ser Val Lys Glu Asn Pro Ala Val 1 5 10 15 Ile Asp Phe
Glu Leu Ala Pro Ile Val Asp Leu Val Arg Asn 20 25 30 67533PRTHomo
sapiens 675Arg Ile Phe Asp Asp Phe Gly Thr His Tyr Phe Thr Ser Gly
Ser Leu 1 5 10 15 Gly Gly Val Tyr Asp Leu Leu Tyr Gln Phe Ser Ser
Glu Glu Leu Lys 20 25 30 Asn 67617PRTHomo sapiens 676Lys Glu Leu
Ser His Leu Pro Ser Leu Tyr Asp Tyr Ser Ala Tyr Arg 1 5 10 15 Arg
67719PRTHomo sapiens 677Arg Arg Tyr Ser Ala Trp Ala Glu Ser Val Thr
Asn Leu Pro Gln Val 1 5 10 15 Ile Lys Gln 67822PRTHomo sapiens
678Lys Val Glu Pro Leu Tyr Glu Leu Val Thr Ala Thr Asp Phe Ala Tyr
1 5 10 15 Ser Ser Thr Val Arg Gln 20 67913PRTHomo sapiens 679Arg
Ser Leu Met Leu His Tyr Glu Phe Leu Gln Arg Val 1 5 10 68019PRTHomo
sapiens 680Lys Tyr Gly Phe Cys Glu Ala Ala Asp Gln Phe His Val Leu
Asp Glu 1 5 10 15 Val Arg Arg 68110PRTHomo sapiens 681Arg Phe Leu
Gln Glu Gln Gly His Arg Ala 1 5 10 68212PRTHomo sapiens 682Arg Lys
Leu Asp Gly Ile Cys Trp Gln Val Arg Gln 1 5 10 68317PRTHomo sapiens
683Arg Ser Leu Pro Val Ser Asp Ser Val Leu Ser Gly Phe Glu Gln Arg
1 5 10 15 Val 68428PRTHomo sapiens 684Arg Gly Thr Val Ile Asp Val
Thr Asp Phe Val Asn Trp Ala Ser Ser 1 5 10 15 Ile Asn Asp Ala Pro
Val Leu Ile Ser Gln Lys Leu 20 25 68531PRTHomo sapiens 685Lys Asn
Pro Arg Glu Asp Tyr Leu Asp Val Tyr Val Phe Gly Val Gly 1 5 10 15
Pro Leu Val Asn Gln Val Asn Ile Asn Ala Leu Ala Ser Lys Lys 20 25
30 68614PRTHomo sapiens 686Arg Gly Asp Ser Gly Gly Pro Leu Ile Val
His Lys Arg Ser 1 5 10 68727PRTHomo sapiens 687Arg His Val Ile Ile
Leu Met Thr Asp Gly Leu His Asn Met Gly Gly 1 5 10 15 Asp Pro Ile
Thr Val Ile Asp Glu Ile Arg Asp 20
25 68832PRTHomo sapiens 688Arg Lys Asn Pro Arg Glu Asp Tyr Leu Asp
Val Tyr Val Phe Gly Val 1 5 10 15 Gly Pro Leu Val Asn Gln Val Asn
Ile Asn Ala Leu Ala Ser Lys Lys 20 25 30 68913PRTHomo sapiens
689Lys Ser Cys Asp Ile Pro Val Phe Met Asn Ala Arg Thr 1 5 10
69028PRTHomo sapiens 690Lys Ser Pro Pro Glu Ile Ser His Gly Val Val
Ala His Met Ser Asp 1 5 10 15 Ser Tyr Gln Tyr Gly Glu Glu Val Thr
Tyr Lys Cys 20 25 69121PRTHomo sapiens 691Lys Thr Asp Cys Leu Ser
Leu Pro Ser Phe Glu Asn Ala Ile Pro Met 1 5 10 15 Gly Glu Lys Lys
Asp 20 69216PRTHomo sapiens 692Lys Arg Ala Gln Leu Gly Asp Leu Pro
Trp Gln Val Ala Ile Lys Asp 1 5 10 15 69312PRTHomo sapiens 693Lys
Ser Leu Glu Cys Leu His Pro Gly Thr Lys Phe 1 5 10 69418PRTHomo
sapiens 694Arg Thr Met Gly Tyr Gln Asp Phe Ala Asp Val Val Cys Tyr
Thr Gln 1 5 10 15 Lys Ala 69512PRTHomo sapiens 695Arg Glu Leu Leu
Ala Leu Ile Gln Leu Glu Arg Glu 1 5 10 69620PRTHomo sapiens 696Arg
Val Pro Glu Ala Arg Pro Asn Ser Met Val Val Glu His Pro Glu 1 5 10
15 Phe Leu Lys Ala 20 6979PRTHomo sapiens 697Arg Leu Phe Trp Glu
Pro Met Lys Val 1 5 69814PRTHomo sapiens 698Arg Asp Val Arg Asp Tyr
Phe Met Pro Cys Pro Gly Arg Gly 1 5 10 69923PRTHomo sapiens 699Lys
Asp Ala Leu Glu Asn Ile Asp Pro Ala Thr Gln Met Met Ile Leu 1 5 10
15 Asn Cys Ile Tyr Phe Lys Gly 20 70027PRTHomo sapiens 700Lys Gly
Leu Ile Lys Asp Ala Leu Glu Asn Ile Asp Pro Ala Thr Gln 1 5 10 15
Met Met Ile Leu Asn Cys Ile Tyr Phe Lys Gly 20 25 70111PRTHomo
sapiens 701Lys Gln Phe Pro Ile Leu Leu Asp Phe Lys Thr 1 5 10
70212PRTHomo sapiens 702Arg Ala Phe Trp Leu Asp Val Ser His Asn Arg
Leu 1 5 10 70327PRTHomo sapiens 703Lys Ala Asp Val Gln Ala His Gly
Glu Gly Gln Glu Phe Ser Ile Thr 1 5 10 15 Cys Leu Val Asp Glu Glu
Glu Met Lys Lys Leu 20 25 70421PRTHomo sapiens 704Lys Ile Leu Gly
Asp Met Gln Pro Gly Asp Tyr Phe Asp Leu Val Leu 1 5 10 15 Phe Gly
Thr Arg Val 20 70515PRTHomo sapiens 705Lys Asn Val Val Phe Val Ile
Asp Ile Ser Gly Ser Met Arg Gly 1 5 10 15 70625PRTHomo sapiens
706Lys Thr Ala Phe Ile Ser Asp Phe Ala Val Thr Ala Asp Gly Asn Ala
1 5 10 15 Phe Ile Gly Asp Ile Lys Asp Lys Val 20 25 70712PRTHomo
sapiens 707Arg Gly His Met Leu Glu Asn His Val Glu Arg Leu 1 5 10
70815PRTHomo sapiens 708Arg Leu Trp Ala Tyr Leu Thr Ile Gln Glu Leu
Leu Ala Lys Arg 1 5 10 15 70912PRTHomo sapiens 709Arg Asn His Met
Gln Tyr Glu Ile Val Ile Lys Val 1 5 10 71015PRTHomo sapiens 710Lys
Ala His Val Ser Phe Lys Pro Thr Val Ala Gln Gln Arg Ile 1 5 10 15
71127PRTHomo sapiens 711Lys Glu Asn Ile Gln Asp Asn Ile Ser Leu Phe
Ser Leu Gly Met Gly 1 5 10 15 Phe Asp Val Asp Tyr Asp Phe Leu Lys
Arg Leu 20 25 71217PRTHomo sapiens 712Lys His Leu Glu Val Asp Val
Trp Val Ile Glu Pro Gln Gly Leu Arg 1 5 10 15 Phe 71316PRTHomo
sapiens 713Lys Leu Trp Ala Tyr Leu Thr Ile Asn Gln Leu Leu Ala Glu
Arg Ser 1 5 10 15 71417PRTHomo sapiens 714Arg Ala Glu Asp His Phe
Ser Val Ile Asp Phe Asn Gln Asn Ile Arg 1 5 10 15 Thr 71522PRTHomo
sapiens 715Arg Phe Leu His Val Pro Asp Thr Phe Glu Gly His Phe Asp
Gly Val 1 5 10 15 Pro Val Ile Ser Lys Gly 20 71610PRTHomo sapiens
716Lys Ile Leu Asp Asp Leu Ser Pro Arg Asp 1 5 10 71713PRTHomo
sapiens 717Lys Ile Pro Lys Pro Glu Ala Ser Phe Ser Pro Arg Arg 1 5
10 71818PRTHomo sapiens 718Lys Ser Pro Glu Gln Gln Glu Thr Val Leu
Asp Gly Asn Leu Ile Ile 1 5 10 15 Arg Tyr 71931PRTHomo sapiens
719Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln Glu
1 5 10 15 Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg
Thr 20 25 30 72014PRTHomo sapiens 720Arg Gly Pro Asp Val Leu Thr
Ala Thr Val Ser Gly Lys Leu 1 5 10 72118PRTHomo sapiens 721Arg Asn
Met Glu Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala 1 5 10 15
Lys Ile 72221PRTHomo sapiens 722Arg Arg Leu Asp Tyr Gln Glu Gly Pro
Pro Gly Val Glu Ile Ser Cys 1 5 10 15 Trp Ser Val Glu Leu 20
72312PRTHomo sapiens 723Lys Ile Val Asp Leu Val Ser Glu Leu Lys Lys
Asp 1 5 10 72414PRTHomo sapiens 724Arg Val Gly Ser Ala Leu Phe Leu
Ser His Asn Leu Lys Phe 1 5 10 72513PRTHomo sapiens 725Lys Thr Val
Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr 1 5 10 72621PRTHomo sapiens
726Arg Asp Ile Pro Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr His
1 5 10 15 Thr Ile Thr Lys Leu 20 7279PRTHomo sapiens 727Arg Val Gln
Val Val Ala Gly Lys Lys 1 5 72810PRTHomo sapiens 728Arg Phe Asn Ala
Leu Gln Tyr Leu Arg Leu 1 5 10 72919PRTHomo sapiens 729Lys Val Ile
Pro Gly Pro Pro Ala Leu Thr Leu Val Pro Ala Glu Leu 1 5 10 15 Val
Arg Ile 73023PRTHomo sapiens 730Lys Ile Thr Gly Thr Met Pro Pro Leu
Pro Leu Glu Ala Thr Gly Leu 1 5 10 15 Ala Leu Ser Ser Leu Arg Leu
20 73117PRTHomo sapiens 731Lys Glu Phe Thr Glu Ala Phe Leu Gly Cys
Pro Ala Ile His Pro Arg 1 5 10 15 Cys 73233PRTHomo sapiens 732Arg
Arg Val Ile Asn Leu Pro Leu Asp Ser Met Ala Ala Pro Trp Glu 1 5 10
15 Thr Gly Asp Thr Phe Pro Asp Val Val Ala Ile Ala Pro Asp Val Arg
20 25 30 Ala 73321PRTHomo sapiens 733Arg Gly Val Phe Phe Ser Val
Asn Ser Trp Thr Pro Asp Ser Met Ser 1 5 10 15 Phe Ile Tyr Lys Ala
20 73419PRTHomo sapiens 734Lys Glu Ile Pro Asp Glu Ile Ser Ile Leu
Leu Leu Gly Val Ala His 1 5 10 15 Phe Lys Gly 73512PRTHomo sapiens
735Lys Thr Val Gln Ala Val Leu Thr Val Pro Lys Leu 1 5 10
73630PRTHomo sapiens 736Arg Ala Leu Tyr Tyr Asp Leu Ile Ser Ser Pro
Asp Ile His Gly Thr 1 5 10 15 Tyr Lys Glu Leu Leu Asp Thr Val Thr
Ala Pro Gln Lys Asn 20 25 30 73714PRTHomo sapiens 737Arg Asp Thr
Asp Thr Gly Ala Leu Leu Phe Ile Gly Lys Ile 1 5 10 73816PRTHomo
sapiens 738Arg Glu Leu Arg Pro Trp Cys Phe Thr Thr Asp Pro Asn Lys
Arg Trp 1 5 10 15 73923PRTHomo sapiens 739Arg Thr Glu Cys Phe Ile
Thr Gly Trp Gly Glu Thr Gln Gly Thr Phe 1 5 10 15 Gly Ala Gly Leu
Leu Lys Glu 20 74016PRTHomo sapiens 740Lys Gly Thr His Cys Asn Gln
Val Glu Val Ile Ala Thr Leu Lys Asp 1 5 10 15 74113PRTHomo sapiens
741Lys Ala Val Gly Tyr Leu Ile Thr Gly Tyr Gln Arg Gln 1 5 10
74229PRTHomo sapiens 742Arg Ala Val Asp Gln Ser Val Leu Leu Met Lys
Pro Glu Ala Glu Leu 1 5 10 15 Ser Val Ser Ser Val Tyr Asn Leu Leu
Thr Val Lys Asp 20 25 74316PRTHomo sapiens 743Arg Ile Gln His Pro
Phe Thr Val Glu Glu Phe Val Leu Pro Lys Phe 1 5 10 15 74415PRTHomo
sapiens 744Arg Asn Glu Leu Ile Pro Leu Ile Tyr Leu Glu Asn Pro Arg
Arg 1 5 10 15 74514PRTHomo sapiens 745Arg Ala Phe Ile Gln Leu Trp
Ala Phe Asp Ala Val Lys Gly 1 5 10 74619PRTHomo sapiens 746Lys Gly
Phe Gly Gly Leu Thr Gly Gln Ile Val Ala Ala Leu Ser Thr 1 5 10 15
Ala Lys Tyr 74711PRTHomo sapiens 747Lys Tyr Gly Phe Tyr Thr His Val
Phe Arg Leu 1 5 10 74831PRTHomo sapiens 748Lys Lys Asp Pro Glu Gly
Leu Phe Leu Gln Asp Asn Ile Val Ala Glu 1 5 10 15 Phe Ser Val Asp
Glu Thr Gly Gln Met Ser Ala Thr Ala Lys Gly 20 25 30 74924PRTHomo
sapiens 749Lys Ala Gln Trp Ala Asn Pro Phe Asp Pro Ser Lys Thr Glu
Asp Ser 1 5 10 15 Ser Ser Phe Leu Ile Asp Lys Thr 20 75011PRTHomo
sapiens 750Lys Gly Trp Val Asp Leu Phe Val Pro Lys Phe 1 5 10
75111PRTHomo sapiens 751Arg Ser Phe Met Leu Leu Ile Leu Glu Arg Ser
1 5 10 75222PRTHomo sapiens 752Lys Glu Phe Ser His Leu Gly Lys Glu
Asp Phe Thr Ser Leu Ser Leu 1 5 10 15 Val Leu Tyr Ser Arg Lys 20
75325PRTHomo sapiens 753Lys His Gln Pro Gln Glu Phe Pro Thr Tyr Val
Glu Pro Thr Asn Asp 1 5 10 15 Glu Ile Cys Glu Ala Phe Arg Lys Asp
20 25 75424PRTHomo sapiens 754Lys Val Pro Thr Ala Asp Leu Glu Asp
Val Leu Pro Leu Ala Glu Asp 1 5 10 15 Ile Thr Asn Ile Leu Ser Lys
Cys 20 75510PRTHomo sapiens 755Lys Ala Val Arg Pro Gly Tyr Pro Lys
Leu 1 5 10 75618PRTHomo sapiens 756Lys Glu Ile Pro Ala Trp Val Pro
Phe Asp Pro Ala Ala Gln Ile Thr 1 5 10 15 Lys Gln 75712PRTHomo
sapiens 757Arg Asn Leu Ala Val Ser Gln Val Val His Lys Ala 1 5 10
75814PRTHomo sapiens 758Lys Ala Ala Ile Ser Gly Glu Asn Ala Gly Leu
Val Arg Ala 1 5 10 75923PRTHomo sapiens 759Lys Thr Ala Phe Ile Ser
Asp Phe Ala Val Thr Ala Asp Gly Asn Ala 1 5 10 15 Phe Ile Gly Asp
Ile Lys Asp 20 7609PRTHomo sapiens 760Lys Val Thr Tyr Asp Val Ser
Arg Asp 1 5 76112PRTHomo sapiens 761Arg Glu Val Ala Phe Asp Leu Glu
Ile Pro Lys Thr 1 5 10 7628PRTHomo sapiens 762Lys Thr Ala Gly Leu
Val Arg Ser 1 5 76312PRTHomo sapiens 763Arg Ser Leu Ala Pro Thr Ala
Ala Ala Lys Arg Arg 1 5 10 76412PRTHomo sapiens 764Lys Glu Val Ser
Phe Asp Val Glu Leu Pro Lys Thr 1 5 10 7658PRTHomo sapiens 765Lys
Ile Gln Glu Asn Val Arg Asn 1 5 7669PRTHomo sapiens 766Arg Ala Leu
Asp Leu Ser Leu Lys Tyr 1 5 76721PRTHomo sapiens 767Arg Leu Ile Gln
Asp Ala Val Thr Gly Leu Thr Val Asn Gly Gln Ile 1 5 10 15 Thr Gly
Asp Lys Arg 20 76811PRTHomo sapiens 768Lys Ser Ser Phe Val Ala Pro
Leu Glu Lys Ser 1 5 10 76913PRTHomo sapiens 769Lys Glu Leu Leu Asp
Thr Val Thr Ala Pro Gln Lys Asn 1 5 10 7709PRTHomo sapiens 770Lys
Phe Gln Leu Pro Gly Gln Lys Leu 1 5 77127PRTHomo sapiens 771Arg Asp
Leu Tyr His Tyr Ile Thr Ser Tyr Val Val Asp Gly Glu Ile 1 5 10 15
Ile Ile Tyr Gly Pro Ala Tyr Ser Gly Arg Glu 20 25 77211PRTHomo
sapiens 772Lys Leu Phe Ile Pro Gln Ile Thr Pro Lys His 1 5 10
77315PRTHomo sapiens 773Asn Ser Ala Thr Gly Glu Glu Ser Ser Thr Ser
Leu Thr Ile Arg 1 5 10 15 77418PRTHomo sapiens 774Lys Phe Gln Gln
Ser Gly Gln Asn Leu Phe Ile Pro Gln Ile Thr Thr 1 5 10 15 Lys His
7759PRTHomo sapiens 775Ile His Pro Ser Tyr Thr Asn Tyr Arg 1 5
7768PRTHomo sapiens 776Phe Gln Leu Ser Glu Thr Asn Arg 1 5
77716PRTHomo sapiens 777Val Ser Ala Pro Ser Gly Thr Gly His Leu Pro
Gly Leu Asn Pro Leu 1 5 10 15 77812PRTHomo sapiens 778Glu Asp Ala
Gly Ser Tyr Thr Leu His Ile Val Lys 1 5 10 77911PRTHomo sapiens
779Arg Thr Leu Phe Ile Phe Gly Val Thr Lys Tyr 1 5 10 78018PRTHomo
sapiens 780Asn Tyr Thr Tyr Ile Trp Trp Leu Asn Gly Gln Ser Leu Pro
Val Ser 1 5 10 15 Pro Arg 78113PRTHomo sapiens 781Gly Val Thr Gly
Tyr Phe Thr Phe Asn Leu Tyr Leu Lys 1 5 10 78216PRTHomo sapiens
782Ser Asn Pro Val Thr Leu Asn Val Leu Tyr Gly Pro Asp Leu Pro Arg
1 5 10 15 78320PRTHomo sapiens 783Asp Val Leu Leu Leu Val His Asn
Leu Pro Gln Asn Leu Thr Gly His 1 5 10 15 Ile Trp Tyr Lys 20
7848PRTHomo sapiens 784Tyr Gly Pro Ala Tyr Ser Gly Arg 1 5
7858PRTHomo sapiens 785Leu Gln Leu Ser Glu Thr Asn Arg 1 5
78610PRTHomo sapiens 786Lys Leu Phe Ile Pro Gln Ile Thr Arg Asn 1 5
10 78716PRTHomo sapiens 787Lys Leu Pro Ile Pro Tyr Ile Thr Ile Asn
Asn Leu Asn Pro Arg Glu 1 5 10 15 78822PRTHomo sapiens 788Ser Glu
Asn Tyr Thr Tyr Ile Trp Trp Leu Asn Gly Gln Ser Leu Pro 1 5 10 15
Val Ser Pro Gly Val Lys 20 7899PRTHomo sapiens 789Ile Leu Ile Leu
Pro Ser Val Thr Arg 1 5 79013PRTHomo sapiens 790Lys Ala Gln Trp Ala
Asn Pro Phe Asp Pro Ser Lys Thr 1 5 10 7918PRTHomo sapiens 791Lys
Phe Leu Asn Asp Val Lys Thr 1 5 79212PRTHomo sapiens 792Lys Asn Ala
Leu Ala Leu Phe Val Leu Pro Lys Glu 1 5 10 79312PRTHomo sapiens
793Arg Asp Phe Asn Gln Phe Ser Ser Gly Glu Lys Asn 1 5 10
79410PRTHomo sapiens 794Lys Gly Tyr Gln Glu Leu Leu Glu Lys Cys 1 5
10 7959PRTHomo sapiens 795Lys Gly Glu Glu Glu Leu Gln Lys Tyr 1 5
7969PRTHomo sapiens 796Lys Phe Ile Tyr Glu Ile Ala Arg Arg 1 5
79717PRTHomo sapiens 797Arg His Pro Phe Leu Tyr Ala Pro Thr Ile Leu
Leu Trp Ala Ala Arg 1 5 10 15 Tyr 79811PRTHomo sapiens 798Arg Thr
Phe Gln Ala Ile Thr Val Thr Lys Leu 1 5 10 7998PRTHomo sapiens
799Lys Leu Thr Thr Leu Glu Arg Gly 1 5 80013PRTHomo sapiens 800Arg
His Pro Gln Leu Ala Val Ser Val Ile Leu Arg Val 1 5 10 80118PRTHomo
sapiens 801Lys Leu Gly Glu Tyr Tyr Leu Gln Asn Ala Phe Leu Val Ala
Tyr Thr 1 5 10 15 Lys Lys 8029PRTHomo sapiens 802Arg Ile Leu Pro
Ser Val Pro Lys Asp 1 5 80318PRTHomo sapiens 803Lys Ala Glu His Pro
Thr Trp Gly Asp Glu Gln Leu Phe Gln Thr Thr 1 5 10 15 Arg Leu
80411PRTHomo sapiens 804Arg Leu Ile Leu Ile Gly Glu Thr Ile Lys Ile
1 5 10 80510PRTHomo sapiens 805Arg Leu Gln Pro Phe Asn Glu Tyr Arg
Lys 1 5 10 80614PRTHomo sapiens 806Glu Leu Ile Glu Glu Leu Val Asn
Ile Thr Gln Asn Gln Lys 1 5 10 80719PRTHomo sapiens 807Leu Ile Gln
Asp Ala Val Thr Gly Leu Thr Val Asn Gly Gln Ile Thr 1 5 10 15 Gly
Asp Lys 8088PRTHomo sapiens 808Gln Ala Leu Glu Glu Phe Gln Lys 1 5
80910PRTHomo sapiens 809Asp Ala Gly Leu Ser Trp Gly Ser Ala Arg 1
5
10 8107PRTHomo sapiens 810Val Phe Gln Phe Leu Glu Lys 1 5
8117PRTHomo sapiens 811Val Gln Thr Ala His Phe Lys 1 5 8129PRTHomo
sapiens 812Ser Asp Leu Glu Val Ala His Tyr Lys 1 5 81314PRTHomo
sapiens 813Val Ser Glu Ala Asp Ser Ser Asn Ala Asp Trp Val Thr Lys
1 5 10 8149PRTHomo sapiens 814Leu Pro Asn Asn Val Leu Gln Glu Lys 1
5 81510PRTHomo sapiens 815Thr Thr Ser Asp Gly Gly Tyr Ser Phe Lys 1
5 10 81611PRTHomo sapiens 816Tyr Glu Asn Tyr Thr Ser Ser Phe Phe
Ile Arg 1 5 10 8178PRTHomo sapiens 817Ala Val Leu His Ile Gly Glu
Lys 1 5 81819PRTHomo sapiens 818Gly Leu Gln Tyr Ala Ala Gln Glu Gly
Leu Leu Ala Leu Gln Ser Glu 1 5 10 15 Leu Leu Arg 81911PRTHomo
sapiens 819Gln Leu Tyr Gly Asp Thr Gly Val Leu Gly Arg 1 5 10
8209PRTHomo sapiens 820Glu Leu Pro Gln Ser Ile Val Tyr Lys 1 5
8218PRTHomo sapiens 821Asn Ile Gln Ser Val Asn Val Lys 1 5
82216PRTHomo sapiens 822Thr Gly Val Ala Val Asn Lys Pro Ala Glu Phe
Thr Val Asp Ala Lys 1 5 10 15 82321PRTHomo sapiens 823His Glu Leu
Thr Asp Glu Glu Leu Gln Ser Leu Phe Thr Asn Phe Ala 1 5 10 15 Asn
Val Val Asp Lys 20 82423PRTHomo sapiens 824Thr Glu Phe Leu Ser Asn
Tyr Leu Thr Asn Val Asp Asp Ile Thr Leu 1 5 10 15 Val Pro Gly Thr
Leu Gly Arg 20 8257PRTHomo sapiens 825Ile Ala Ile Asp Leu Phe Lys 1
5 82610PRTHomo sapiens 826Thr Val Gln Ala Val Leu Thr Val Pro Lys 1
5 10 82711PRTHomo sapiens 827Leu Ile Glu Asn Gly Tyr Phe His Pro
Val Lys 1 5 10 8287PRTHomo sapiens 828Phe Leu Pro Cys Glu Asn Lys 1
5 82917PRTHomo sapiens 829His Pro Trp Ile Val His Trp Asp Gln Leu
Pro Gln Tyr Gln Leu Asn 1 5 10 15 Arg 83010PRTHomo sapiens 830Gln
Gly His Asn Ser Val Phe Leu Ile Lys 1 5 10 8317PRTHomo sapiens
831His Phe Gln Asn Leu Gly Lys 1 5 83216PRTHomo sapiens 832Ile Ala
Pro Gln Leu Ser Thr Glu Glu Leu Val Ser Leu Gly Glu Lys 1 5 10 15
83310PRTHomo sapiens 833Asp Ala Asp Pro Asp Thr Phe Phe Ala Lys 1 5
10 83410PRTHomo sapiens 834Val Asn His Val Thr Leu Ser Gln Pro Lys
1 5 10 83510PRTHomo sapiens 835His Tyr Gly Gly Leu Thr Gly Leu Asn
Lys 1 5 10 83613PRTHomo sapiens 836Asn Cys Ser Phe Ser Ile Ile Tyr
Pro Val Val Ile Lys 1 5 10 83722PRTHomo sapiens 837Ala Gln Pro Val
Gln Val Ala Glu Gly Ser Glu Pro Asp Gly Phe Trp 1 5 10 15 Glu Ala
Leu Gly Gly Lys 20 8389PRTHomo sapiens 838Leu Asp Phe His Phe Ser
Ser Asp Arg 1 5 8398PRTHomo sapiens 839Thr Leu Asn Ala Tyr Asp His
Arg 1 5 84014PRTHomo sapiens 840Glu Val Phe Ser Lys Pro Ile Ser Trp
Glu Glu Leu Leu Gln 1 5 10 84111PRTHomo sapiens 841Asn Phe Pro Ser
Pro Val Asp Ala Ala Phe Arg 1 5 10 8429PRTHomo sapiens 842Thr Leu
Phe Ile Phe Gly Val Thr Lys 1 5 8439PRTHomo sapiens 843Tyr Tyr Gly
Tyr Thr Gly Ala Phe Arg 1 5 8447PRTHomo sapiens 844Gln Val Phe Ala
Val Gln Arg 1 5 84510PRTHomo sapiens 845Asp Phe Asn Gln Phe Ser Ser
Gly Glu Lys 1 5 10 84613PRTHomo sapiens 846Ser Val Ser Leu Pro Ser
Leu Asp Pro Ala Ser Ala Lys 1 5 10 8479PRTHomo sapiens 847Gly Asn
Gly Leu Thr Trp Ala Glu Lys 1 5 84822PRTHomo sapiens 848Gly Ala Val
His Val Val Val Ala Glu Thr Asp Tyr Gln Ser Phe Ala 1 5 10 15 Val
Leu Tyr Leu Glu Arg 20 84914PRTHomo sapiens 849Thr Ser Glu Ser Thr
Gly Ser Leu Pro Ser Pro Phe Leu Arg 1 5 10 85012PRTHomo sapiens
850Tyr Ile Ser Pro Asp Gln Leu Ala Asp Leu Tyr Lys 1 5 10
85110PRTHomo sapiens 851Glu Ser Asp Thr Ser Tyr Val Ser Leu Lys 1 5
10 8528PRTHomo sapiens 852Ile Leu Asp Asp Leu Ser Pro Arg 1 5
85311PRTHomo sapiens 853Ser Gly Val Asp Leu Ala Asp Ser Asn Gln Lys
1 5 10 85412PRTHomo sapiens 854Asp Thr Asp Thr Gly Ala Leu Leu Phe
Ile Gly Lys 1 5 10 8559PRTHomo sapiens 855His Tyr Phe Ile Ala Ala
Val Glu Arg 1 5 85610PRTHomo sapiens 856Asp Leu His Leu Ser Asp Val
Phe Leu Lys 1 5 10 85712PRTHomo sapiens 857Asp Pro Thr Phe Ile Pro
Ala Pro Ile Gln Ala Lys 1 5 10 8587PRTHomo sapiens 858Ala Gly Ile
Thr Ile Pro Arg 1 5 8599PRTHomo sapiens 859Ile Ala Gln Tyr Tyr Tyr
Thr Phe Lys 1 5 86010PRTHomo sapiens 860Tyr Asn Ser Gln Leu Leu Ser
Phe Val Arg 1 5 10 86119PRTHomo sapiens 861Ala Asn Asp Gln Tyr Leu
Thr Ala Ala Ala Leu His Asn Leu Asp Glu 1 5 10 15 Ala Val Lys
8629PRTHomo sapiens 862Phe Gln Ser Val Phe Thr Val Thr Arg 1 5
86314PRTHomo sapiens 863Leu Gln Val Asn Thr Pro Leu Val Gly Ala Ser
Leu Leu Arg 1 5 10 86412PRTHomo sapiens 864Asp Glu Ile Pro His Asn
Asp Ile Ala Leu Leu Lys 1 5 10 86510PRTHomo sapiens 865His Ala Thr
Leu Ser Leu Ser Ile Pro Arg 1 5 10 86610PRTHomo sapiens 866Thr Gly
Ile Ser Pro Leu Ala Leu Ile Lys 1 5 10 8677PRTHomo sapiens 867Ile
Leu Pro Ser Val Pro Lys 1 5 86812PRTHomo sapiens 868Leu Pro Ala Thr
Glu Lys Pro Val Leu Leu Ser Lys 1 5 10 86911PRTHomo sapiens 869Thr
Phe Leu Thr Val Tyr Trp Thr Pro Glu Arg 1 5 10 87016PRTHomo sapiens
870Gly Asp Thr Tyr Pro Ala Glu Leu Tyr Ile Thr Gly Ser Ile Leu Arg
1 5 10 15 87113PRTHomo sapiens 871Ser Leu Asp Phe Thr Glu Leu Asp
Val Ala Ala Glu Lys 1 5 10 87214PRTHomo sapiens 872Val Glu Leu Ala
Pro Leu Pro Ser Trp Gln Pro Val Gly Lys 1 5 10 8737PRTHomo sapiens
873Gly Pro Gly Glu Asp Phe Arg 1 5 8749PRTHomo sapiens 874Ile Leu
Asn Ile Phe Gly Val Ile Lys 1 5 87515PRTHomo sapiens 875Ile Ser Gln
Gly Glu Ala Asp Ile Asn Ile Ala Phe Tyr Gln Arg 1 5 10 15
8768PRTHomo sapiens 876Phe Thr Ile Thr Ala Gly Ser Lys 1 5
8777PRTHomo sapiens 877Ile Leu Asp Gly Gly Asn Lys 1 5 87813PRTHomo
sapiens 878Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu Asp Arg 1 5
10 8799PRTHomo sapiens 879Ser Asp Gly Ala Lys Pro Gly Pro Arg 1 5
8806PRTHomo sapiens 880Gln Asp Leu Gly Trp Lys 1 5 8817PRTHomo
sapiens 881Ser Ile Leu Phe Leu Gly Lys 1 5 88221PRTHomo sapiens
882Ile Glu Val Asn Glu Ser Gly Thr Val Ala Ser Ser Ser Thr Ala Val
1 5 10 15 Ile Val Ser Ala Arg 20 88320PRTHomo sapiens 883Leu Leu
Ala Pro Ser Asp Ser Pro Glu Trp Leu Ser Phe Asp Val Thr 1 5 10 15
Gly Val Val Arg 20 8848PRTHomo sapiens 884Ile Glu Val Ile Ile Thr
Leu Lys 1 5 8857PRTHomo sapiens 885Asp Tyr Trp Ser Thr Val Lys 1 5
88612PRTHomo sapiens 886Trp Ile Leu Thr Ala Ala His Thr Leu Tyr Pro
Lys 1 5 10 88712PRTHomo sapiens 887Ser Pro Glu Ala Glu Asp Pro Leu
Gly Val Glu Arg 1 5 10 88816PRTHomo sapiens 888Ser Gly Ala Gln Ala
Thr Trp Thr Glu Leu Pro Trp Pro His Glu Lys 1 5 10 15 8897PRTHomo
sapiens 889Tyr Ser His Tyr Asn Glu Arg 1 5 89020PRTHomo sapiens
890Glu Val Pro Leu Ser Ala Leu Thr Asn Ile Leu Ser Ala Gln Leu Ile
1 5 10 15 Ser His Trp Lys 20 89122PRTHomo sapiens 891Ala Ala Leu
Ala Ala Phe Asn Ala Gln Asn Asn Gly Ser Asn Phe Gln 1 5 10 15 Leu
Glu Glu Ile Ser Arg 20 89220PRTHomo sapiens 892Ile Val Leu Ser Leu
Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 1 5 10 15 Glu Gln Ala
Arg 20 89318PRTHomo sapiens 893Glu Asn Pro Ala Val Ile Asp Phe Glu
Leu Ala Pro Ile Val Asp Leu 1 5 10 15 Val Arg 89411PRTHomo sapiens
894Asn Val Asn Gln Ser Leu Leu Glu Leu His Lys 1 5 10 8959PRTHomo
sapiens 895Glu Ile Gly Glu Leu Tyr Leu Pro Lys 1 5 89617PRTHomo
sapiens 896Asn Lys Pro Gly Val Tyr Thr Asp Val Ala Tyr Tyr Leu Ala
Trp Ile 1 5 10 15 Arg 89713PRTHomo sapiens 897Gln Asn Tyr His Gln
Asp Ser Glu Ala Ala Ile Asn Arg 1 5 10 8986PRTHomo sapiens 898Val
Thr Phe Glu Tyr Arg 1 5 8999PRTHomo sapiens 899Asp Leu Pro His Ile
Thr Val Asp Arg 1 5 90019PRTHomo sapiens 900Gly Ser Leu Val Gln Ala
Ser Glu Ala Asn Leu Gln Ala Ala Gln Asp 1 5 10 15 Phe Val Arg
9015PRTHomo sapiens 901Phe Leu Tyr His Lys 1 5 9028PRTHomo sapiens
902Leu Gln Asp Ala Gly Val Tyr Arg 1 5 9038PRTHomo sapiens 903Ile
Asn Pro Ala Ser Leu Asp Lys 1 5 9048PRTHomo sapiens 904Leu Glu Glu
His Tyr Glu Leu Arg 1 5 90511PRTHomo sapiens 905Thr Ser Asp Gln Ile
His Phe Phe Phe Ala Lys 1 5 10 90611PRTHomo sapiens 906Ala Thr Leu
Ser Ala Ala Pro Ser Asn Pro Arg 1 5 10 90713PRTHomo sapiens 907Glu
Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg 1 5 10 90814PRTHomo
sapiens 908Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro Arg
1 5 10 90912PRTHomo sapiens 909Gly Glu Val Thr Tyr Thr Thr Ser Gln
Val Ser Lys 1 5 10 91011PRTHomo sapiens 910Ser Leu Gln Ala Phe Val
Ala Val Ala Ala Arg 1 5 10 91115PRTHomo sapiens 911Gly Pro Glu Asp
Gln Asp Ile Ser Ile Ser Phe Ala Trp Asp Lys 1 5 10 15 91212PRTHomo
sapiens 912Tyr Val Val Ile Ser Gln Gly Leu Asp Lys Pro Arg 1 5 10
91315PRTHomo sapiens 913Gly Thr Ala Glu Trp Leu Ser Phe Asp Val Thr
Asp Thr Val Arg 1 5 10 15 91419PRTHomo sapiens 914Ala His Gln Leu
Ala Ile Asp Thr Tyr Gln Glu Phe Glu Glu Thr Tyr 1 5 10 15 Ile Pro
Lys 91510PRTHomo sapiens 915Thr Ala Val Thr Ala Asn Leu Asp Ile Arg
1 5 10 91616PRTHomo sapiens 916Trp Ser Ala Gly Leu Thr Ser Ser Gln
Val Asp Leu Tyr Ile Pro Lys 1 5 10 15 9177PRTHomo sapiens 917Gln
Ile Asn Ser Tyr Val Lys 1 5 91812PRTHomo sapiens 918Gly Phe Gln Ala
Leu Gly Asp Ala Ala Asp Ile Arg 1 5 10 9196PRTHomo sapiens 919Asn
Glu Ile Trp Tyr Arg 1 5 9207PRTHomo sapiens 920Val Leu Glu Pro Thr
Leu Lys 1 5 92111PRTHomo sapiens 921Ala Leu Asn Ser Ile Ile Asp Val
Tyr His Lys 1 5 10 92225PRTHomo sapiens 922Glu Thr Pro Glu Gly Ala
Glu Ala Lys Pro Trp Tyr Glu Pro Ile Tyr 1 5 10 15 Leu Gly Gly Val
Phe Gln Leu Glu Lys 20 25 92310PRTHomo sapiens 923Leu Asn Ile Gly
Tyr Ile Glu Asp Leu Lys 1 5 10 92410PRTHomo sapiens 924Asp Ile Pro
His Trp Leu Asn Pro Thr Arg 1 5 10 92517PRTHomo sapiens 925Asn Glu
Ile Val Phe Pro Ala Gly Ile Leu Gln Ala Pro Phe Tyr Thr 1 5 10 15
Arg 92616PRTHomo sapiens 926Ala Glu His Pro Thr Trp Gly Asp Glu Gln
Leu Phe Gln Thr Thr Arg 1 5 10 15 92714PRTHomo sapiens 927Ser Trp
Asn Glu Pro Leu Tyr His Leu Val Thr Glu Val Arg 1 5 10 92811PRTHomo
sapiens 928Ile Pro Lys Pro Glu Ala Ser Phe Ser Pro Arg 1 5 10
92911PRTHomo sapiens 929Asp Asp Leu Tyr Val Ser Asp Ala Phe His Lys
1 5 10 93026PRTHomo sapiens 930Gln Arg Pro Pro Asp Leu Asp Thr Ser
Ser Asn Ala Val Asp Leu Leu 1 5 10 15 Phe Phe Thr Asp Glu Ser Gly
Asp Ser Arg 20 25 93116PRTHomo sapiens 931Gly Gln Val Pro Glu Asn
Glu Ala Asn Val Val Ile Thr Thr Leu Lys 1 5 10 15 93218PRTHomo
sapiens 932Phe Thr Gly Ser Gln Pro Phe Gly Gln Gly Val Glu His Ala
Thr Ala 1 5 10 15 Asn Lys 93318PRTHomo sapiens 933Leu Glu Pro Leu
Tyr Ser Ala Ser Gly Pro Gly Leu Arg Pro Leu Val 1 5 10 15 Ile Lys
93414PRTHomo sapiens 934Ile Gln His Pro Phe Thr Val Glu Glu Phe Val
Leu Pro Lys 1 5 10 9358PRTHomo sapiens 935Thr Glu Gln Ala Ala Val
Ala Arg 1 5 93613PRTHomo sapiens 936Leu Phe Tyr Ala Asp His Pro Phe
Ile Phe Leu Val Arg 1 5 10 9378PRTHomo sapiens 937Thr Ser Tyr Gln
Val Tyr Ser Lys 1 5 93813PRTHomo sapiens 938Asn Val Ile Gln Ile Ser
Asn Asp Leu Glu Asn Leu Arg 1 5 10 93923PRTHomo sapiens 939Ala Phe
Leu Glu Val Asn Glu Glu Gly Ser Glu Ala Ala Ala Ser Thr 1 5 10 15
Ala Val Val Ile Ala Gly Arg 20 94018PRTHomo sapiens 940Leu His Glu
Ala Phe Ser Pro Val Ser Tyr Gln His Asp Leu Ala Leu 1 5 10 15 Leu
Arg 94118PRTHomo sapiens 941Gly Pro Ile Thr Ser Ala Ala Glu Leu Asn
Asp Pro Gln Ser Ile Leu 1 5 10 15 Leu Arg 94214PRTHomo sapiens
942Ala Val Asp Ile Pro Gly Leu Glu Ala Ala Thr Pro Tyr Arg 1 5 10
94310PRTHomo sapiens 943Val Pro Leu Ala Leu Phe Ala Leu Asn Arg 1 5
10 9449PRTHomo sapiens 944Val Val Gly Gly Leu Val Ala Leu Arg 1 5
94511PRTHomo sapiens 945Asn His Tyr Thr Glu Ser Ile Ser Val Ala Lys
1 5 10 94624PRTHomo sapiens 946Val Val Leu Ser Ser Gly Ser Gly Pro
Gly Leu Asp Leu Pro Leu Val 1 5 10 15 Leu Gly Leu Pro Leu Gln Leu
Lys 20 94722PRTHomo sapiens 947Ala Leu Ala Leu Pro Pro Leu Gly Leu
Ala Pro Leu Leu Asn Leu Trp 1 5 10 15 Ala Lys Pro Gln Gly Arg 20
9488PRTHomo sapiens 948Ile Pro Ser Asn Pro Ser His Arg 1 5
94915PRTHomo sapiens 949Ala Asn Leu Ile Asn Asn Ile Phe Glu Leu Ala
Gly Leu Gly Lys 1 5 10 15 95011PRTHomo sapiens 950Asn Glu Pro Glu
Glu Thr Pro Ser Ile Glu Lys 1 5 10 9519PRTHomo sapiens 951Val Pro
Ser His Ala Val Val Ala Arg 1 5 95219PRTHomo sapiens 952Gly Gly Leu
Phe Ala Asp Ile Ala Ser His Pro Trp Gln Ala Ala Ile 1 5 10 15 Phe
Ala Lys 9537PRTHomo sapiens 953Ser Pro Gln Ala Phe Tyr Arg 1 5
95419PRTHomo sapiens 954Ser Ser Asn Asn Pro His Ser Pro Ile Val Glu
Glu Phe Gln Val Pro 1 5 10 15 Tyr Asn Lys 95510PRTHomo sapiens
955Leu Ile Glu Ile Ala Asn His Val Asp Lys 1 5 10 9568PRTHomo
sapiens 956Gly Tyr Gln Glu Leu Leu Glu Lys 1 5 95720PRTHomo sapiens
957Ser Val Val Leu Ile Pro Leu Gly Ala Val Asp Asp Gly Glu His Ser
1 5 10 15 Gln Asn Glu Lys 20 95818PRTHomo sapiens 958Ser Glu Thr
Glu Ile His Gln Gly Phe Gln His Leu His Gln Leu Phe 1 5 10 15 Ala
Lys 9598PRTHomo sapiens
959Ala Glu Ile Glu Tyr Leu Glu Lys 1 5 9609PRTHomo sapiens 960Val
Gly Val Ile Ser Phe Ala Gln Lys 1 5 96117PRTHomo sapiens 961Val Phe
Gln Tyr Ile Asp Leu His Gln Asp Glu Phe Val Gln Thr Leu 1 5 10 15
Lys 9628PRTHomo sapiens 962Val Leu Ser Ser Ile Glu Gln Lys 1 5
9636PRTHomo sapiens 963Thr Leu Pro Phe Ser Arg 1 5 96416PRTHomo
sapiens 964Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser
Gly Lys 1 5 10 15 96510PRTHomo sapiens 965Tyr Trp Gly Val Ala Ser
Phe Leu Gln Lys 1 5 10 96614PRTHomo sapiens 966Ser Tyr Thr Ile Thr
Gly Leu Gln Pro Gly Thr Asp Tyr Lys 1 5 10 96724PRTHomo sapiens
967Ala Leu Asn Phe Gly Gly Ile Gly Val Val Val Gly His Glu Leu Thr
1 5 10 15 His Ala Phe Asp Asp Gln Gly Arg 20 96818PRTHomo sapiens
968Ser Val Pro Val Thr Lys Pro Val Pro Val Thr Lys Pro Ile Thr Val
1 5 10 15 Thr Lys 9697PRTHomo sapiens 969Ile Tyr Leu Gln Pro Gly
Arg 1 5 97015PRTHomo sapiens 970Glu Trp Val Ala Ile Glu Ser Asp Ser
Val Gln Pro Val Pro Arg 1 5 10 15 97125PRTHomo sapiens 971Asp Leu
Tyr His Tyr Ile Thr Ser Tyr Val Val Asp Gly Glu Ile Ile 1 5 10 15
Ile Tyr Gly Pro Ala Tyr Ser Gly Arg 20 25 9728PRTHomo sapiens
972Glu Cys Glu Glu Leu Glu Glu Lys 1 5 9738PRTHomo sapiens 973Ser
Thr Pro Ser Leu Thr Thr Lys 1 5 97410PRTHomo sapiens 974Ala Leu Leu
Leu Gly Trp Val Pro Thr Arg 1 5 10 97514PRTHomo sapiens 975Ile Ala
Leu Gly Gly Leu Leu Phe Pro Ala Ser Asn Leu Arg 1 5 10 97611PRTHomo
sapiens 976Gly Tyr Val Ile Ile Lys Pro Leu Val Trp Val 1 5 10
97714PRTHomo sapiens 977Asn Thr Gly Val Ile Ser Val Val Thr Thr Gly
Leu Asp Arg 1 5 10 97810PRTHomo sapiens 978Ser Glu Arg Pro Pro Ile
Phe Glu Ile Arg 1 5 10 97925PRTHomo sapiens 979Thr Ala His Ile Ser
Gly Leu Pro Pro Ser Thr Asp Phe Ile Val Tyr 1 5 10 15 Leu Ser Gly
Leu Ala Pro Ser Ile Arg 20 25 9809PRTHomo sapiens 980Ala Thr Asn
Ala Thr Leu Asp Pro Arg 1 5 98110PRTHomo sapiens 981Gln Thr Leu Ser
Trp Thr Val Thr Pro Lys 1 5 10 9829PRTHomo sapiens 982Asp Ile Ile
Lys Pro Asp Pro Pro Lys 1 5 9836PRTHomo sapiens 983His Val Val Gln
Leu Arg 1 5 98411PRTHomo sapiens 984Asn Thr Val Ile Ser Val Asn Pro
Ser Thr Lys 1 5 10 9857PRTHomo sapiens 985Ile Leu Thr Pro Glu Val
Arg 1 5 9867PRTHomo sapiens 986Glu Leu Ala Asn Thr Ile Lys 1 5
9879PRTHomo sapiens 987Leu Ser Ile Pro Gln Ile Thr Thr Lys 1 5
98817PRTHomo sapiens 988Ser Val Gln Asn Asp Ser Gln Ala Ile Ala Glu
Val Leu Asn Gln Leu 1 5 10 15 Lys 98914PRTHomo sapiens 989Ala Leu
Pro Gly Glu Gln Gln Pro Leu His Ala Leu Thr Arg 1 5 10 99018PRTHomo
sapiens 990Gly Thr Tyr Leu Tyr Asn Asp Cys Pro Gly Pro Gly Gln Asp
Thr Asp 1 5 10 15 Cys Arg 99119PRTHomo sapiens 991Asn Asn Gln Leu
Val Ala Gly Tyr Leu Gln Gly Pro Asn Val Asn Leu 1 5 10 15 Glu Glu
Lys 9928PRTHomo sapiens 992Phe Gly Ser Asp Asp Glu Gly Arg 1 5
99313PRTHomo sapiens 993Phe Ala Thr Thr Phe Tyr Gln His Leu Ala Asp
Ser Lys 1 5 10 99410PRTHomo sapiens 994Glu Thr Leu Ala Leu Leu Ser
Thr His Arg 1 5 10 9956PRTHomo sapiens 995Thr Tyr Asn Val Asp Lys 1
5 9968PRTHomo sapiens 996Leu Phe Ile Pro Gln Ile Thr Arg 1 5
99719PRTHomo sapiens 997Asn Ala Val Val Gln Gly Leu Glu Gln Pro His
Gly Leu Val Val His 1 5 10 15 Pro Leu Arg 99810PRTHomo sapiens
998Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg 1 5 10 9999PRTHomo
sapiens 999Val Ile Ala Val Asn Glu Val Gly Arg 1 5 100010PRTHomo
sapiens 1000Ser Leu Ser Gln Gln Ile Glu Asn Ile Arg 1 5 10
10017PRTHomo sapiens 1001Ser Val Asp Glu Ala Leu Arg 1 5
100212PRTHomo sapiens 1002Phe Val Phe Gly Thr Thr Pro Glu Asp Ile
Leu Arg 1 5 10 100310PRTHomo sapiens 1003Thr Gly Tyr Tyr Phe Asp
Gly Ile Ser Arg 1 5 10 10049PRTHomo sapiens 1004Ile Gly Lys Pro Ala
Pro Asp Phe Lys 1 5 10057PRTHomo sapiens 1005Phe Ile Val Gly Phe
Thr Arg 1 5 100614PRTHomo sapiens 1006Asp Ser Pro Val Leu Ile Asp
Phe Phe Glu Asp Thr Glu Arg 1 5 10 100713PRTHomo sapiens 1007Val
Ala Pro Gly Val Ala Asn Pro Gly Thr Pro Leu Ala 1 5 10
100816PRTHomo sapiens 1008Asn Tyr Phe Thr Ser Val Ala His Pro Asn
Leu Phe Ile Ala Thr Lys 1 5 10 15 10099PRTHomo sapiens 1009Asp Thr
Tyr Val Ser Ser Phe Pro Arg 1 5 10109PRTHomo sapiens 1010His Ser
His Glu Ser Gln Asp Leu Arg 1 5 101116PRTHomo sapiens 1011Val Ser
Phe Ser Ser Pro Leu Val Ala Ile Ser Gly Val Ala Leu Arg 1 5 10 15
10127PRTHomo sapiens 1012Trp Gly Ala Ala Pro Tyr Arg 1 5
101314PRTHomo sapiens 1013Ala Leu Phe Leu Asp Ala Leu Gly Pro Pro
Ala Val Thr Arg 1 5 10 10149PRTHomo sapiens 1014Ala Lys Pro Ala Leu
Glu Asp Leu Arg 1 5 10158PRTHomo sapiens 1015Val Asn Phe Thr Glu
Ile Gln Lys 1 5 101617PRTHomo sapiens 1016Gly Val Thr Ser Val Ser
Gln Ile Phe His Ser Pro Asp Leu Ala Ile 1 5 10 15 Arg 101710PRTHomo
sapiens 1017Leu Leu Asp Ser Leu Pro Ser Asp Thr Arg 1 5 10
101810PRTHomo sapiens 1018Phe Gln Pro Thr Leu Leu Thr Leu Pro Arg 1
5 10 10198PRTHomo sapiens 1019Thr Leu Tyr Ser Ser Ser Pro Arg 1 5
102015PRTHomo sapiens 1020Gly Asp Ser Gly Gly Ala Phe Ala Val Gln
Asp Pro Asn Asp Lys 1 5 10 15 10216PRTHomo sapiens 1021Leu Gln Val
Leu Gly Lys 1 5 10229PRTHomo sapiens 1022Leu Phe Ile Pro Gln Ile
Thr Pro Lys 1 5 102313PRTHomo sapiens 1023Ile Arg Pro His Thr Phe
Thr Gly Leu Ser Gly Leu Arg 1 5 10 102411PRTHomo sapiens 1024Leu
Ser Asn Glu Asn His Gly Ile Ala Gln Arg 1 5 10 10259PRTHomo sapiens
1025Leu His Lys Pro Gly Val Tyr Thr Arg 1 5 102617PRTHomo sapiens
1026Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile Ile
1 5 10 15 Lys 102710PRTHomo sapiens 1027Thr Gln Ile Asp Ser Pro Leu
Ser Gly Lys 1 5 10 102811PRTHomo sapiens 1028Ala Thr Trp Ser Gly
Ala Val Leu Ala Gly Arg 1 5 10 102918PRTHomo sapiens 1029Val Ala
Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn 1 5 10 15
Pro Lys 103013PRTHomo sapiens 1030Cys Gln Cys Leu Gln Thr Leu Gln
Gly Ile His Leu Lys 1 5 10 103110PRTHomo sapiens 1031Leu Leu Asp
Phe Glu Phe Ser Ser Gly Arg 1 5 10 103214PRTHomo sapiens 1032Ile
Leu Asn Thr Pro Asn Cys Ala Leu Gln Ile Val Ala Arg 1 5 10
10338PRTHomo sapiens 1033Gly Leu Phe Ile Ile Asp Gly Lys 1 5
10349PRTHomo sapiens 1034Glu His Ser Ser Leu Ala Phe Trp Lys 1 5
10358PRTHomo sapiens 1035Thr Phe Thr Leu Leu Asp Pro Lys 1 5
103613PRTHomo sapiens 1036Ala His Gln Leu Ala Ile Asp Thr Tyr Gln
Glu Phe Arg 1 5 10 103711PRTHomo sapiens 1037Ala Gln Glu Thr Ser
Gly Glu Glu Ile Ser Lys 1 5 10 103810PRTHomo sapiens 1038Leu Ser
Ile Thr Gly Thr Tyr Asp Leu Lys 1 5 10 103911PRTHomo sapiens
1039Glu Ala Leu Val Pro Leu Val Ala Asp His Lys 1 5 10
104012PRTHomo sapiens 1040Cys Arg Pro Ile Asn Ala Thr Leu Ala Val
Glu Lys 1 5 10 104112PRTHomo sapiens 1041Leu Thr Leu Leu Ala Pro
Leu Asn Ser Val Phe Lys 1 5 10 104216PRTHomo sapiens 1042Ala Asp
Leu Phe Tyr Asp Val Glu Ala Leu Asp Leu Glu Ser Pro Lys 1 5 10 15
104310PRTHomo sapiens 1043Arg Ile Pro Leu Asp Leu Val Pro Lys Thr 1
5 10 104420PRTHomo sapiens 1044Lys Glu Asn Pro Ala Val Ile Asp Phe
Glu Leu Ala Pro Ile Val Asp 1 5 10 15 Leu Val Arg Asn 20
104520PRTHomo sapiens 1045Lys Tyr Asn Pro Val Val Ile Asp Phe Glu
Met Gln Pro Ile His Glu 1 5 10 15 Val Leu Arg His 20 104613PRTHomo
sapiens 1046Arg Gly Asp Ser Gly Gly Pro Leu Ile Val His Lys Arg 1 5
10 104733PRTHomo sapiens 1047Arg Val Leu Lys Asp Gln Val Asn Thr
Phe Asp Asn Ile Phe Ile Ala 1 5 10 15 Pro Val Gly Ile Ser Thr Ala
Met Gly Met Ile Ser Leu Gly Leu Lys 20 25 30 Gly 104817PRTHomo
sapiens 1048Lys Pro Leu Leu Asn Asp Ser Arg Met Leu Leu Ser Pro Asp
Gln Lys 1 5 10 15 Val 104915PRTHomo sapiens 1049Lys Glu Asp Phe Thr
Ser Leu Ser Leu Val Leu Tyr Ser Arg Lys 1 5 10 15 105014PRTHomo
sapiens 1050Trp Asn Phe Ala Tyr Trp Ala Ala His Gln Pro Trp Ser Arg
1 5 10 105111PRTHomo sapiens 1051Ser Glu Tyr Gly Ala Ala Leu Ala
Trp Glu Lys 1 5 10 105213PRTHomo sapiens 1052Leu Trp Ala Tyr Leu
Thr Ile Gln Glu Leu Leu Ala Lys 1 5 10 10538PRTHomo sapiens 1053Leu
Leu Glu Val Pro Glu Gly Arg 1 5 105410PRTHomo sapiens 1054Leu Thr
Thr Val Asp Ile Val Thr Leu Arg 1 5 10 10556PRTHomo sapiens 1055Thr
Leu Ala Phe Val Arg 1 5 10569PRTHomo sapiens 1056Asn Ser Asp Gln
Glu Ile Asp Phe Lys 1 5 105725PRTHomo sapiens 1057Tyr His Phe Glu
Ala Leu Ala Asp Thr Gly Ile Ser Ser Glu Phe Tyr 1 5 10 15 Asp Asn
Ala Asn Asp Leu Leu Ser Lys 20 25 105820PRTHomo sapiens 1058Ile Leu
Leu Leu Gly Thr Ala Val Glu Ser Ala Trp Gly Asp Glu Gln 1 5 10 15
Ser Ala Phe Arg 20 10596PRTHomo sapiens 1059Tyr Asn Gln Leu Leu Arg
1 5 106014PRTHomo sapiens 1060Val Pro Gly Leu Tyr Tyr Phe Thr Tyr
His Ala Ser Ser Arg 1 5 10 10618PRTHomo sapiens 1061Tyr Gly Ile Glu
Glu His Gly Lys 1 5 106213PRTHomo sapiens 1062Gln Val Cys Ala Asp
Pro Ser Glu Glu Trp Val Gln Lys 1 5 10 106311PRTHomo sapiens
1063Asp Pro Asn Gly Leu Pro Pro Glu Ala Gln Lys 1 5 10 10648PRTHomo
sapiens 1064Glu Thr Leu Leu Gln Asp Phe Arg 1 5 106516PRTHomo
sapiens 1065Ile Ile Glu Val Glu Glu Glu Gln Glu Asp Pro Tyr Leu Asn
Asp Arg 1 5 10 15 10667PRTHomo sapiens 1066Glu Leu Cys Leu Asp Pro
Lys 1 5 106711PRTHomo sapiens 1067Asn Gln Ser Pro Val Leu Glu Pro
Val Gly Arg 1 5 10 10688PRTHomo sapiens 1068Phe Phe Gln Tyr Asp Thr
Trp Lys 1 5 106913PRTHomo sapiens 1069Ser Leu Gln Asn Ala Ser Ala
Ile Glu Ser Ile Leu Lys 1 5 10
* * * * *