U.S. patent application number 10/126468 was filed with the patent office on 2002-11-28 for system, method, and computer software product for linked window interfaces.
Invention is credited to Jevons, Luis, Kaushikkar, Shantanu V..
Application Number | 20020175949 10/126468 |
Document ID | / |
Family ID | 26921061 |
Filed Date | 2002-11-28 |
United States Patent
Application |
20020175949 |
Kind Code |
A1 |
Kaushikkar, Shantanu V. ; et
al. |
November 28, 2002 |
System, method, and computer software product for linked window
interfaces
Abstract
Systems, methods, and computer program products are described
for providing a graphical user interface (GUI) that may include a
first openable window of image features constituting, for example,
a pseudo-image of a scanned probe array. The image features each
have one or more characteristics representing one or more
hybridization reactions associated with a probe of the probe array.
The GUI also has a second openable window including data features,
each relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array.
This second window may be, for example, a scatter plot of
hybridization intensities of probes to two or more labeled samples.
The GUI further includes a third openable window including
descriptive features such as rows of a spreadsheet. Each row may
include descriptive elements associated with a probe. When a user
selects a feature from any of the two or more windows, a
corresponding feature in at least one other of the two or more
windows is highlighted.
Inventors: |
Kaushikkar, Shantanu V.;
(San Jose, CA) ; Jevons, Luis; (Sunnyvale,
CA) |
Correspondence
Address: |
CHIEF INTELLECTUAL PATENT COUNSEL
AFFYMETRIX, INC.
3380 CENTRAL EXPRESSWAY
SANTA CLARA
CA
95051
US
|
Family ID: |
26921061 |
Appl. No.: |
10/126468 |
Filed: |
April 19, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10126468 |
Apr 19, 2002 |
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PCT/US01/26390 |
Aug 22, 2001 |
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60226999 |
Aug 22, 2000 |
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60286578 |
Apr 26, 2001 |
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Current U.S.
Class: |
715/781 |
Current CPC
Class: |
G01N 2021/6441 20130101;
B01J 2219/00675 20130101; B01J 2219/00533 20130101; B01J 2219/00612
20130101; B01J 2219/00605 20130101; B01J 2219/00677 20130101; G01N
27/44721 20130101; G01N 2021/6419 20130101; G01N 21/6452 20130101;
G01N 2021/6471 20130101; B01J 2219/00527 20130101; C40B 50/14
20130101; G16B 25/00 20190201; B01J 2219/00659 20130101; G01N
2035/00158 20130101; G01N 2021/6421 20130101; B01J 2219/00596
20130101; G01N 27/44717 20130101; B01J 2219/00695 20130101; B01J
2219/00707 20130101; G01N 2035/0494 20130101; B01J 2219/00689
20130101; B01J 2219/00702 20130101; B01J 2219/00585 20130101; G16B
45/00 20190201 |
Class at
Publication: |
345/781 |
International
Class: |
G09G 005/00 |
Claims
What is claimed is:
1. A user interface, comprising: a first openable window having a
plurality of first image features, each having one or more
characteristics representing one or more hybridization reactions
associated with a probe of a probe array; a second openable window
having a plurality of data features, each relating to one or more
quantifications of one or more hybridization reactions associated
with a probe of the probe array; and a third openable window having
a plurality of descriptive features, each including one or more
descriptive elements associated with a probe of the probe
array.
2. The user interface of claim 1, wherein the probe array comprises
a spotted array.
3. The user interface of claim 1, wherein the probe array comprises
a synthesized array.
4. The user interface of claim 1, wherein the first, second, and
third openable windows are all open in the interface at a same
time.
5. The user interface of claim 1, further comprising: a fourth
openable window having a plurality of second image features, each
having one or more characteristics representing one or more
hybridization reactions associated with a probe of the probe
array.
6. The user interface of claim 5, wherein the first image features
are generated based on emissions of a first wavelength and the
second image features are generated based on emissions of a second
wavelength different from the first wavelength.
7. The user interface of claim 1, wherein the one or more
characteristics of the plurality of first image features include a
chromatic value representing degree, efficiency, or intensity of
hybridization.
8. The user interface of claim 7, wherein the chromatic value is a
hue, brightness, lightness, or saturation value.
9. The user interface of claim 1, wherein the one or more
characteristics of the plurality of first image features include an
intensity value representing degree, efficiency, or intensity of
hybridization.
10. The user interface of claim 9, wherein the intensity value
includes a gray-scale value.
11. The user interface of claim 1, wherein: the plurality of first
image features comprises a pseudo-image of the array.
12. The user interface of claim 1, wherein the plurality of data
features each represent a quantification of degree, efficiency, or
intensity of hybridization of a probe based on the probe
hybridizing with none, one or a plurality of targets.
13. The user interface of claim 12, wherein the second openable
window comprises a two-dimensional scatter plot wherein the
plurality of data features comprises marks on the scanner plot,
each representing a quantification of degree, efficiency, or
intensity of hybridization of a probe with first and second
targets.
14. The user interface of claim 12, wherein the second openable
window comprises a histogram wherein the plurality of data features
comprises bars, each representing a quantification of a number of
probes having in common a range of degree, efficiency, or intensity
of hybridization with one or more targets.
15. The user interface of claim 12, wherein the second openable
window comprises a graphical representation selected from the group
consisting of a scatter plot, histogram, bar graph, or line
graph.
16. The user interface of claim 1, wherein the plurality of
descriptive features comprises rows of a spreadsheet wherein each
row includes one or more descriptive elements associated with a
probe.
17. The user interface of claim 1, wherein the descriptive elements
comprise any one or more of the group of elements consisting of
absolute image intensity value, relative image intensity value,
user-supplied data related to the probe, biological information
related to the probe; probe identifier, probe x-coordinate
identifier, probe y-coordinate identifier, probe-related data,
probe data links, pin identifier, well plate identifier.
18. The user interface of claim 17, wherein the probe data links
include links to remotely or locally stored user-supplied data
related to the probe or links to remotely or locally stored
biological information related to the probe.
19. The user interface of claim 17, wherein the probe-related data
include any one or more datum selected from the group consisting of
chromosome location of a gene or EST represented by the probe, band
location on the chromosome, or SNP or other marker identifying the
location on the chromosome.
20. The user interface of claim 1, wherein when a user selects a
first image feature associated with a first probe, a data feature
or a descriptive feature associated with the first probe, or both,
are highlighted.
21. The user interface of claim 1, wherein when a user selects a
data feature associated with a first probe, a first image feature
or a descriptive feature associated with the first probe, or both,
are highlighted.
22. The user interface of claim 1, wherein: when a user selects a
descriptive feature associated with a first probe, a first image
feature or a data feature associated with the first probe, or both,
are highlighted.
23. A user interface, comprising: two or more windows selected from
the group consisting of a first window having a plurality of image
features, each having one or more characteristics representing one
or more hybridization reactions associated with a probe of a probe
array; a second window having a plurality of data features, each
relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array;
and a third window having a plurality of descriptive features, each
including one or more descriptive elements associated with a probe
of the probe array; wherein, when a user selects a feature from any
of the two or more windows, a corresponding feature in at least one
other of the two or more windows is highlighted.
24. A computer program product comprising: (a) an image processor
constructed and arranged to process image data based on scanning a
probe array; and (b) a GUI manager constructed and arranged to
provide two or more windows selected from the group consisting of
(i) a first window having a plurality of image features based on
the processed image data, each having one or more characteristics
representing one or more hybridization reactions associated with a
probe of the probe array, (ii) a second window having a plurality
of data features, each relating to one or more quantifications of
one or more hybridization reactions associated with a probe of the
probe array, and (iii) a third window having a plurality of
descriptive features, each including one or more descriptive
elements associated with a probe of the probe array.
25. The computer program product of claim 24, wherein: when a user
selects a feature from any of the two or more windows, the GUI
manager further is constructed and arranged to cause a
corresponding feature in at least one other of the two or more
windows to be highlighted.
26. The computer program product of claim 24, wherein the probe
array is a spotted array.
27. The computer program product of claim 24, wherein the probe
array is a synthesized array.
28. A computer program product comprising: a GUI manager
constructed and arranged to provide two or more windows selected
from the group consisting of (i) a first window having a plurality
of image features, each having one or more characteristics
representing one or more hybridization reactions associated with a
probe of a probe array, (ii) a second window having a plurality of
data features, each relating to one or more quantifications of one
or more hybridization reactions associated with a probe of the
probe array, and (iii) a third window having a plurality of
descriptive features, each including one or more descriptive
elements associated with a probe of the probe array.
29. A method comprising the steps of: (a) providing image data
based on scanning a probe array; and (b) providing in a graphical
user interface two or more windows selected from the group
consisting of (i) a first window having a plurality of image
features based on the image data, each having one or more
characteristics representing one or more hybridization reactions
associated with a probe of a probe array, (ii) a second window
having a plurality of data features, each relating to one or more
quantifications of one or more hybridization reactions associated
with a probe of the probe array, and (iii) a third window having a
plurality of descriptive features, each including one or more
descriptive elements associated with a probe of the probe
array.
30. The method of claim 29, further comprising the steps of: (c)
receiving a user selection of a feature from any of the two or more
windows; and (d) causing a corresponding feature in at least one
other of the two or more windows to be highlighted.
31. A scanning system, comprising: (a) a scanner constructed and
arranged to scan a probe array to generate image data; (b) an image
processor constructed and arranged to process the image data; and
(c) a GUI manager constructed and arranged to provide two or more
windows selected from the group consisting of (i) a first window
having a plurality of image features based on the processed image
data, each having one or more characteristics representing one or
more hybridization reactions associated with a probe of the probe
array, (ii) a second window having a plurality of data features,
each relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array,
and (iii) a third window having a plurality of descriptive
features, each including one or more descriptive elements
associated with a probe of the probe array.
32. A scanning system, comprising: a scanner constructed and
arranged to scan a probe array to generate image data; a computer;
and a computer program product that, when executed on the computer,
performs a method comprising the steps of: (a) processing the image
data, and (b) providing in a graphical user interface two or more
windows selected from the group consisting of (i) a first window
having a plurality of image features based on the processed image
data, each having one or more characteristics representing one or
more hybridization reactions associated with a probe of a probe
array, (ii) a second window having a plurality of data features,
each relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array,
and (iii) a third window having a plurality of descriptive
features, each including one or more descriptive elements
associated with a probe of the probe array.
33. The method of claim 32, wherein: the method performed by the
computer program product further includes the steps of (c)
receiving a user selection of a feature from any of the two or more
windows, and (d) causing a corresponding feature in at least one
other of the two or more windows to be highlighted.
34. A computer system for providing a user interface with a scanner
for scanning a probe array to generate image data, comprising: a
first window means for providing image feature means having one or
more characteristics representing one or more hybridization
reactions associated with probe means of the probe array; a second
window means for providing a data feature means related to one or
more quantification means of one or more hybridization reactions
associated with probe means of the probe array; and a third window
means for providing descriptive feature means including one or more
descriptive elements associated with probe means of the probe
array.
35. A computer system for providing a user interface with a scanner
for scanning a probe array, the system being programmed to display
image features having one or more characteristics representing one
or more hybridization reactions associated with a probe of the
probe array, data features related to one or more quantifications
of one or more hybridization reactions associated with a probe of
the probe array, and descriptive features including one or more
descriptive elements associated with a probe of the probe
array.
36. A computer program product comprising a GUI manager constructed
and arranged to provide display regions for displaying image
features representing hybridization associated with a probe of a
probe array, data features related to quantifying the hybridization
associated with a probe of the probe array, and descriptive
features associated with a probe of the probe array.
37. A computer program product comprising a GUI manager means for
providing window means for displaying image feature means
representing hybridization means associated with a probe means of a
probe array, data feature means related to quantifying
hybridization means associated with probe means of the probe array,
and descriptive feature means associated with probe means of the
probe array.
Description
RELATED APPLICATIONS
[0001] The present application relates to and claims priority from
U.S. Provisional Patent Application Ser. No. 60/226,999, titled
"System, Method, and Product for Linked Window Interface," filed
Aug. 22, 2000; U.S. Provisional Patent Application Serial No.
60/286,578, titled "System, Method, and Product for Scanning of
Biological Materials," filed Apr. 26, 2001; and PCT Application
PCT/US01/26390 filed on, Aug. 22, 2001, all of which are hereby
incorporated herein by reference in their entireties for all
purposes.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to computer systems, methods,
and products for analyzing and displaying scanned images of
high-density arrays of biological materials.
[0004] 2. Related Art
[0005] Synthesized probe arrays, such as Affymetrix.RTM.
GeneChip.RTM. arrays, have been used to generate unprecedented
amounts of information about biological systems. For example, a
commercially available GeneChip.RTM. array set from Affymetrix,
Inc. of Santa Clara, Calif., is capable of monitoring the
expression levels of approximately 6,500 murine genes and expressed
sequence tags (EST's). Experimenters can quickly design follow-on
experiments with respect to genes, EST's, or other biological
materials of interest by, for example, producing in their own
laboratories microscope slides containing dense arrays of probes
using the Affymetrix.RTM. 417.TM. Arrayer or other spotting
devices.
[0006] Analysis of data from experiments with synthesized and/or
spotted probe arrays may lead to the development of new drugs and
new diagnostic tools. In some conventional applications, this
analysis begins with the capture of fluorescent signals indicating
hybridization of labeled target samples with probes on synthesized
or spotted probe arrays. The devices used to capture these signals
often are referred to as scanners, an example of which is the
Affymetrix.RTM. 428.TM. Scanner from Affymetrix.
[0007] There is a great demand in the art for methods for
organizing, accessing, analyzing, and displaying the vast amount of
information collected by scanning microarrays. Computer-based
systems and methods have been developed to assist a user to obtain
and visualize the vast amounts of information generated by the
scanners. These commercial and academic software applications
typically provide such information as intensities of hybridization
reactions or comparisons of hybridization reactions. This
information may be displayed to a user in graphical form.
SUMMARY OF THE INVENTION
[0008] The present invention includes a system, a method, and a
computer program product for controlling an optical scanner.
Systems, methods, and computer program products are described with
respect to some embodiments for providing a graphical user
interface (GUI). The GUI may include a first openable window of
image features constituting, for example, a pseudo-image of a
scanned probe array. The term "pseudo-image" is used in this
context to mean that the image features provide a graphical
representation of the probes of a probe array that typically are
based on emissions from probe-target pairs, lack of emissions from
probes that have not hybridized with targets, and information about
the location of the probes on the probe array. The word "openable"
is used in this context to mean that the window may be opened, e.g.
by a user, so as to be displayed in the GUI, but may also be closed
or otherwise not displayed. The image features have one or more
characteristics representing one or more hybridization reactions
associated with a probe of the probe array.
[0009] The GUI of these embodiments also has a second openable
window including data features, each relating to one or more
quantifications of one or more hybridization reactions associated
with a probe of the probe array. This second window may be, for
example, a scatter plot of hybridization intensities of probes to
two or more labeled samples. The GUI further includes a third
openable window including descriptive features such as rows of a
spreadsheet. Each row may include descriptive elements associated
with a probe. In some implementations, when a user selects a
feature from any of the two or more windows, a corresponding
feature in at least one other of the two or more windows is
highlighted. For example, a user may select an image feature in the
first window (e.g., a spot representing a probe of a spotted
array), thereby causing a spot in the scatter plot and a row in the
spreadsheet to be highlighted. The spot in the scatter plot and the
spreadsheet row provide information about the probe corresponding
to the image feature selected by the user in the first window.
[0010] The probes may be those of a spotted probe array such as may
be generated, for example, by an Affymetrix.TM. 417.TM. or 427.TM.
Arrayer. As another non-limiting example, the probes may be those
synthesized on a synthesized array such as an Affymetrix.RTM.
GeneChip.RTM. array.
[0011] With respect to the first window, the graphically
represented probes have one or more characteristics indicative of
the efficiency or intensity of hybridization associated with the
corresponding probe. For example, the intensity or another visual
characteristic of the image features graphically representing
probes may be varied to indicate the efficiency or intensity of
hybridization. With respect to the example of the second window
constituting a scatter plot, the plot may show along one axis the
intensity of emissions from a first label such as a dye that
fluoresces in response a first excitation source. The scatter plot
may show along another axis the intensity of emissions from a
second dye that fluoresces in response the same or another
excitation source. The scatter plot need not be limited to two
dimensions, as when, for example, a third dye is associated with
probe-target pairs hybridized on the probe array. Any form of
labeling may be used, and many types of graphs may be employed that
provide, for example, visual comparisons between two or more sets
of hybridization data.
[0012] A third of the two or more windows may include a table,
spreadsheet, or other textual or graphical representation of
information related to probes in the probe array. In some
implementations, for example, a third window may include a
spreadsheet having rows (or, in other aspects, columns, or
combinations thereof) containing any of a variety of data. For
example, the data may relate to the experiment that produced the
hybridization intensities represented by a pseudo-image in the
first window, e.g., the type of dye or dyes used in the experiment.
The data may also include links to sources, such as on the Internet
or another database source, containing information about the probes
and/or the targets that hybridized with the probes. As yet another
non-limiting example, the data may include statistical information
about the absolute or relative intensities of the probes. As a
further non-limiting example, the data may include notes, labels,
or other information provided by the user.
[0013] In some implementations, two or more of the windows are
simultaneously displayed to the user on a display device. The user
may select a graphical element of one of the simultaneously
displayed windows and a corresponding graphical element on another
of the two or more windows is highlighted. The highlighting may be
done in accordance with any of a variety of known techniques, such
as by changing the font and/or color of foreground or background,
or by providing special effects such as blinking.
[0014] A fourth window may also be opened in some implementations.
This fourth window may, like the first window, include image
features having one or more characteristics representing one or
more hybridization reactions associated with a probe of the probe
array. For example, the image features of the first window may have
characteristics (such as color or gray-scale intensity)
representing the degree, efficiency, or intensity of hybridization
of a first sample labeled with a first fluorescent dye to the
probes of a spotted array. The image features of the second window
may have characteristics representing the degree, efficiency, or
intensity of hybridization of a second sample labeled with a second
fluorescent dye to the probes of the same spotted array. As another
example, the image features of the first window may represent the
degree, efficiency, or intensity of hybridization of a first sample
labeled with a first fluorescent dye to the probes of a first
synthesized array, and the mage features of the second window may
represent the degree, efficiency, or intensity of hybridization of
a second sample labeled with a the same or another fluorescent dye
to the probes of a second synthesized array having probes
essentially the same as the probes of the first synthesized
array.
[0015] The characteristics of the image features of the first
and/or fourth window may include a chromatic value representing
degree, efficiency, or intensity of hybridization. For example, the
chromatic value may be a hue (color), brightness, lightness, or
saturation value. The characteristic may also, or in addition, be
an intensity value. The intensity value may be, for example, a
gray-scale value.
[0016] The second openable window may, in some embodiments, include
a histogram wherein the plurality of data features comprises bars,
each representing a quantification of a number of probes having in
common a range of degree, efficiency, or intensity of hybridization
with one or more targets. The second openable window may also be
any other kind of representation of statistical information about
absolute or relative hybridization of probes such as may be
conveyed, for example, by a scatter plot (as noted), a bar graph,
or a line graph.
[0017] With respect to the third openable window, the descriptive
features may, as one example, constitute rows of a spreadsheet.
Each row may include one or more descriptive elements associated
with a probe. Non-limiting examples of descriptive elements include
any one or combination of two or more of the following: absolute
image intensity value, relative image intensity value,
user-supplied data related to the probe, biological information
related to the probe; probe identifier, probe x-coordinate
identifier, probe y-coordinate identifier, probe-related data,
probe data links, pin identifier, and/or well plate identifier. The
probe data links may include links to remotely or locally stored
user-supplied data related to the probe, and/or links to remotely
or locally stored biological information related to the probe. The
probe-related data may include chromosome location of a gene or EST
represented by the probe, band location on the chromosome, and/or
SNP or other marker identifying the location on the chromosome.
[0018] In accordance with other embodiments, a user interface is
described that includes any combination of two or more of the
following windows: a first window having a plurality of image
features, each having one or more characteristics representing one
or more hybridization reactions associated with a probe of a probe
array; a second window having a plurality of data features, each
relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array;
and a third window having a plurality of descriptive features, each
including one or more descriptive elements associated with a probe
of the probe array. In these embodiments, when a user selects a
feature from any of the two or more windows, a corresponding
feature in at least one other of the two or more windows is
highlighted.
[0019] In accordance with yet other embodiments, a computer program
product is described. This product includes an image processor that
processes image data based on scanning a probe array, and a GUI
manager constructed and arranged to provide two or more windows.
The windows may be any combination of the following: (i) a first
window having a plurality of image features based on the processed
image data, each having one or more characteristics representing
one or more hybridization reactions associated with a probe of the
probe array, (ii) a second window having a plurality of data
features, each relating to one or more quantifications of one or
more hybridization reactions associated with a probe of the probe
array, and/or (iii) a third window having a plurality of
descriptive features, each including one or more descriptive
elements associated with a probe of the probe array. When a user
selects a feature from any of the two or more windows, the GUI
manager may, in some implementations, cause a corresponding feature
in at least one other of the two or more windows to be
highlighted.
[0020] Also described is a computer program product having a GUI
manager that provides two or more windows. These windows may be any
combination of (i) a first window having a plurality of image
features, each having one or more characteristics representing one
or more hybridization reactions associated with a probe of the
probe array, (ii) a second window having a plurality of data
features, each relating to one or more quantifications of one or
more hybridization reactions associated with a probe of the probe
array, and (iii) a third window having a plurality of descriptive
features, each including one or more descriptive elements
associated with a probe of the probe array.
[0021] In accordance with yet other embodiments, a method is
described that includes providing image data based on scanning a
probe array and providing, in a graphical user interface, two or
more windows. These windows are selected from the group consisting
of (i) a first window having a plurality of image features based on
the image data, each having one or more characteristics
representing one or more hybridization reactions associated with a
probe of a probe array, (ii) a second window having a plurality of
data features, each relating to one or more quantifications of one
or more hybridization reactions associated with a probe of the
probe array, and (iii) a third window having a plurality of
descriptive features, each including one or more descriptive
elements associated with a probe of the probe array.
[0022] Also included in the following description is a scanning
system that includes a scanner that scans a probe array to generate
image data, an image processor that processes the image data, and a
GUI manager that provides two or more windows. These windows may be
any combination of the following: (i) a first window having a
plurality of image features based on the processed image data, each
having one or more characteristics representing one or more
hybridization reactions associated with a probe of the probe array,
(ii) a second window having a plurality of data features, each
relating to one or more quantifications of one or more
hybridization reactions associated with a probe of the probe array,
and (iii) a third window having a plurality of descriptive
features, each including one or more descriptive elements
associated with a probe of the probe array.
[0023] Yet another described embodiment is a scanning system. This
system includes a scanner that scans a probe array to generate
image data, a computer, and a computer program product. When
executed on the computer, the computer program product performs a
method comprising the steps of processing the image data and
providing, in a graphical user interface, two or more windows.
These windows may be any combination of the following: (i) a first
window having a plurality of image features based on the processed
image data, each having one or more characteristics representing
one or more hybridization reactions associated with a probe of a
probe array, (ii) a second window having a plurality of data
features, each relating to one or more quantifications of one or
more hybridization reactions associated with a probe of the probe
array, and(iii) a third window having a plurality of descriptive
features, each including one or more descriptive elements
associated with a probe of the probe array.
[0024] Generally, one advantage provided by the preceding and other
embodiments is that data regarding probe-target hybridization, and
the probes associated with the hybridization reactions, may be
simultaneously displayed to a user in a variety of forms. These
forms may include, for example, two or more of a pseudo-image of
probe-target hybridization (and probes that did not hybridize with
targets); a statistical representation of absolute or relative
hybridization (such as in a scatter plot); and/or a table of
processed, derived, calculated, retrieved, and/or user-supplied
information related to the probes. By selecting a feature
corresponding to a probe or probes in one of these windows, other
information related to the same probe or probes may be highlighted
in the same or other window or windows for the benefit of the
user.
[0025] According to yet another embodiment, a computer system for
providing a user interface with a scanner for scanning a probe
array to generate image data includes two or more window means.
These window means may include a first window means for providing
image feature means having one or more characteristics representing
one or more hybridization reactions associated with probe means of
a probe array; and a second window means for providing a data
feature means related to one or more quantification means of said
one or more hybridization reactions associated with probe means of
the probe array. These window means may also include a third window
means for providing descriptive feature means including one or more
descriptive elements associated with probe means of the probe
array.
[0026] According to yet another embodiment, a computer system for
providing a user interface with a scanner for scanning a probe
array is programmed to display image features having one or more
characteristics representing one or more hybridization reactions
associated with a probe of the probe array, data features related
to one or more quantifications of one or more hybridization
reactions associated with a probe of the probe array, and
descriptive features including one or more descriptive elements
associated with a probe of the probe array.
[0027] According to yet another embodiment, a computer program
product includes a GUI manager. The GUI manager is constructed and
arranged to provide display regions for displaying image features
representing hybridization associated with a probe of a probe
array, data features related to quantifying the hybridization
associated with a probe of the probe array, and descriptive
features associated with a probe of the probe array.
[0028] According to yet another embodiment, a computer program
includes a GUI manager for providing window means for displaying
image feature means representing hybridization means associated
with a probe means of a probe array, for displaying data feature
means related to quantifying hybridization means associated with
probe means of the probe array, and for displaying descriptive
feature means associated with probe means of the probe array.
[0029] The above embodiments, implementations, and aspects are not
necessarily inclusive or exclusive of each other and may be
combined in any manner that is nonconflicting and otherwise
possible, whether they be presented in association with a same, or
a different, aspect of the invention. The description of one
embodiment, implementation, or aspect is not intended to be
limiting with respect to other embodiments or implementations.
Also, any one or more function, step, operation, or technique
described elsewhere in this specification may, in alternative
embodiments or implementations, be combined with any one or more
function, step, operation, or technique described in the summary.
Thus, the above embodiments, implementations, and aspects are
illustrative rather than limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] FIG. 1 is a simplified schematic diagram of one embodiment
of networked systems for generating, sharing, and processing probe
array data among computers on a network, including an arrayer
system for generating spotted probe arrays and scanner systems for
scanning spotted and synthesized probe arrays.
[0031] FIG. 2 is a functional block diagram of one embodiment of a
user computer of the networked computers of FIG. 1 suitable for
controlling the arrayer of FIG. 1 to produce spotted arrays.
[0032] FIG. 3A is a graphical representation of data records in one
embodiment of a data file suitable for storing data regarding
spotted arrays produced in cooperation with the user computer of
FIG. 2 and the arrayer of FIG. 1.
[0033] FIG. 3B is a graphical representation of a microscope slide
including illustrative embodiments of spotted arrays produced in
cooperation with the user computer of FIG. 2 and the arrayer of
FIG. 1.
[0034] FIG. 4 is a simplified graphical representation of selected
components of one embodiment of a scanner of FIG. 1 suitable for
scanning arrays.
[0035] FIG. 5A is a perspective view of a simplified exemplary
configuration of a scanning arm portion of the scanner of FIG.
4.
[0036] FIG. 5B is a top planar view of the scanning arm of FIG. 5A
as it scans biological features on one embodiment of a spotted
array being moved by a translation stage under the arm's arcuate
path.
[0037] FIG. 6A is a graphical representation of one embodiment of a
probe feature showing bidirectional scanning lines such as may be
implemented using the scanning arm of FIGS. 5A and 5B.
[0038] FIG. 6B is an illustrative plot of pixel clock pulses
aligned with the scanned probe feature of FIG. 6A to show
illustrative radial position sampling points.
[0039] FIG. 6C is an illustrative plot of sampled analog emission
voltages aligned with the pixel clock pulses of FIG. 6B.
[0040] FIG. 7 is a functional block diagram of one embodiment of a
scanner system of FIG. 1.
[0041] FIG. 8 is functional block diagram of one embodiment of a
scanner control and analysis application (i.e., computer program
product).
[0042] FIG. 9 is an illustrative implementation of a graphical user
interface employed in cooperation with the application of FIG.
8.
[0043] The described features will be more clearly appreciated from
the following detailed description when taken in conjunction with
the accompanying drawings. In the drawings, like reference numerals
indicate like structures or method steps and the leftmost digit of
a reference numeral indicates the number of the figure in which the
referenced element first. In functional block diagrams, rectangles
generally indicate functional elements, parallelograms generally
indicate data, and rectangles with a pair of double borders
generally indicate predefined functional elements. In method flow
charts, rectangles generally indicate method steps and diamond
shapes generally indicate decision elements. All of these
conventions, however, are intended to be typical or illustrative,
rather than limiting.
DETAILED DESCRIPTION
[0044] Systems, methods, and software products to display data from
experiments with synthesized and/or spotted arrays are described
herein with respect to illustrative, non-limiting, implementations.
Various other alternatives, modifications and equivalents are
possible. For example, while certain systems, methods, and computer
software products are described using exemplary embodiments with
reference to spotted arrays analyzed and displayed using
Affymetrix.RTM. scanners and/or Affymetrix software, the systems,
methods, and products of the present invention are not so limited.
For example, they generally may be applied with respect to many
other probe arrays, including many types of parallel biological
assays.
Probe Arrays
[0045] For example, certain systems, methods, and computer software
products are described herein using exemplary implementations for
acquiring, analyzing, and/or displaying data from arrays of
biological materials produced by the Affymetrix.RTM. 417.TM. or
427.TM. Arrayers available from Affymetrix, Inc. Other illustrative
implementations may be referred to in relation to data from
experiments with Affymetrix.RTM. GeneChip.RTM. arrays. However,
these systems, methods, and products may be applied with respect to
many other types of probe arrays and, more generally, with respect
to numerous parallel biological assays produced in accordance with
other conventional technologies and/or produced in accordance with
techniques that may be developed in the future. For example,
aspects of the systems, methods, and products described herein may,
in some implementations, be applied to parallel assays of nucleic
acids, PCR products generated from cDNA clones, proteins,
antibodies, or many other biological materials. These materials may
be disposed on slides (as typically used for spotted arrays), on
substrates employed for GeneChip.RTM. arrays, or on beads, optical
fibers, or other substrates, supports, or media (all or any of
which may hereafter generally and collectively be referred to as
"substrates"). Some implementations of synthesized arrays, their
preparation, substrates, and the like are described in U.S. Pat.
Nos. 5,744,305 and 5,445,934, which are hereby incorporated herein
by reference in their entireties for all purposes. Moreover, with
respect to some implementations in which the context so indicates
or allows, the probes need not be immobilized in or on a substrate,
and, if immobilized, need not be disposed in regular patterns or
arrays. For convenience, the term "probe array" will generally be
used broadly hereafter to refer to all of these types of arrays and
parallel biological assays.
[0046] For convenience, an array made by depositing or positioning
pre-synthesized or pre-selected probes on a substrate, or by
depositing/positioning techniques that may be developed in the
future, is hereafter referred to as a "spotted array." Typically,
but not necessarily, spotted arrays are commercially fabricated on
microscope slides. These arrays often consist of liquid spots
containing biological material of potentially varying compositions
and concentrations. For instance, a spot in the array may include a
few strands of short polymers, such as oligonucleotides in a water
solution, or it may include a high concentration of long strands of
polymers, such as complex proteins. The Affymetrix.RTM. 417.TM. and
427.TM. Arrayers, noted above, are devices that deposit densely
packed arrays of biological material on a microscope slide in
accordance with these techniques. Aspects of these, and other, spot
arrayers are described in U.S. Pat. Nos. 6,121,048, 6,040,193 and
6,136,269, in PCT applications Nos. PCT/US99/00730 (International
Publication Number WO99/36760) and PCT/US 01/04285, in U.S. patent
applications Ser. Nos. 09/122,216, 09/501,099, and 09/862,177, and
in U.S. Provisional Patent Application Serial No. 60/288,403, all
of which are hereby incorporated by reference in their entireties
for all purposes. Other techniques for depositing or positioning
biological probes on a substrate, i.e., creating spotted arrays,
also exist. For example, U.S. Pat. No. 6,040,193 to Winkler, et al.
is directed to processes for dispensing drops of biological
material. The '193 patent, and U.S. Pat. No. 5,885,837 to Winkler,
also describe separating reactive regions of a substrate from each
other by inert regions and spotting on the reactive regions. The
'193 and '837 patents are hereby incorporated by reference in their
entireties. Other techniques for producing spotted arrays are based
on ejecting jets of biological material. Some implementations of
the jetting technique use devices such as syringes or piezo
electric pumps to propel the biological material.
[0047] Spotted arrays typically are used in conjunction with tagged
biological samples such as cells, proteins, genes or EST's, other
DNA sequences, or other biological elements. These samples,
referred to herein as "targets," typically are processed so that
they are spatially associated with certain probes in the probe
array. In one non-limiting implementation, for example, one or more
chemically tagged biological samples, i.e., the targets, are
distributed over the probe array. Some targets hybridize with at
least partially complementary probes and remain at the probe
locations, while non-hybridized targets are washed away. These
hybridized targets, with their "tags" or "labels," are thus
spatially associated with the targets' complementary probes. The
associated probe and target may sometimes be referred to as a
"probe-target pair." Detection of these pairs can serve a variety
of purposes, such as to determine whether a target nucleic acid has
a nucleotide sequence identical to or different from a specific
reference sequence. See, for example, U.S. Pat. No. 5,837,832 to
Chee, et al. Other uses include gene expression monitoring and
evaluation (see, e.g., U.S. Pat. No. 5,800,992 to Fodor, et al.;
U.S. Pat. No. 6,040,138 to Lockhart, et al.; and International App.
No. PCT/US98/15151, published as WO99/05323, to Balaban, et al.),
genotyping (U.S. Pat. No. 5,856,092 to Dale, et al.), or other
detection of nucleic acids. The '832', '992', '138, and '092
patents, and publication WO99/05323, are incorporated by reference
herein in their entirety for all purposes.
[0048] To ensure proper interpretation of the term "probe" as used
herein, it is noted that contradictory conventions exist in the
relevant literature. The word "probe" is used in some contexts in
the literature to refer not to the biological material that is
deposited on a substrate, as described above, but to what has been
referred to herein as the "target." To avoid confusion, the term
"probe" is used herein to refer to compounds such as those
deposited on a substrate to create spotted arrays, or
oligonucleotides on synthesized arrays, as non-limiting
examples.
Probe Array Experiment Systems
[0049] FIG. 1 is a simplified schematic diagram of illustrative
systems for generating, sharing, and processing data derived from
experiments using probe arrays (i.e., spotted arrays and/or
synthesized arrays). More particularly, an illustrative arrayer
system 148 and illustrative scanner systems 150A and 150B
(collectively, scanner systems 150) are shown. Arrayer system 148
includes arrayer 120 that may be any type of arrayer for depositing
probes to create spotted arrays such as, for example, the
Affymetrix 417.TM. or 427.TM. Arrayers noted above. Further details
of illustrative arrayers are provided in U.S. patent application
Ser. No. 09/682,076, hereby incorporated by reference in its
entirety for all purposes. In the presently illustrated example,
data may be communicated among user computer 100A of system 148,
user computers 100B and 100C of systems 150, and Laboratory
Information Management (LIMS) server 120 over network 125. LIMS
server 120 and associated software generally provides data
capturing, tracking, and analysis functions from a centralized
infrastructure. Aspects of a LIMS are described in U.S. Provisional
Patent Application Nos. 60/220,587 and 60/273,231, both of which
are hereby incorporated by reference herein for all purposes. LIMS
server 120 and network 125 are optional, and the systems in other
implementations may include a scanner for spotted arrays and not
synthesized arrays, or vice versa. Also, rather than employing
separate user computers 100A and 100B to operate and process data
from an arrayer and scanner, respectively, as in the illustrated
implementation, a single computer may be used for all of these
purposes in other implementations. More generally, a large variety
of computer and/or network architectures and designs may be
employed, and it will be understood by those of ordinary skill in
the relevant art that many components of typical computer network
systems are not shown in FIG. 1 for sake of clarity.
User Computer 100A
[0050] As shown in FIG. 1 and noted above, arrayer 120 operates in
the illustrated implementation under computer control, e.g., under
the control of user computer 100A. Although computer 100A is shown
in FIG. 1 for clarity as being directly coupled to arrayer 120, it
may alternatively be coupled to arrayer 120 over a local-area,
wide-area, or other network, including an intranet and/or the
Internet.
[0051] FIG. 2 is a functional block diagram showing an illustrative
implementation of computer 100. Computer 100 may be a personal
computer, a workstation, a server, or any other type of computing
platform now available or that may be developed in the future.
Typically, computer 100A includes known components such as
processor (e.g., CPU) 205, operating system 210, system memory 220,
memory storage devices 225, graphical user interface (GUI)
controller 215, and input-output controllers 230, all of which
typically communicate in accordance with known techniques such as
via system bus 204. It will be understood by those skilled in the
relevant art that there are many possible configurations of the
components of computer 100A and that some components that may
typically be included in computer 100A are not shown, such as cache
memory, a data backup unit, and many other devices.
[0052] Input-output controllers 230 could include any of a variety
of known devices for accepting and processing information from a
user, whether a human or a machine, whether local or remote. Such
devices include, for example, modem cards, network interface cards,
sound cards, or other types of controllers for any of a variety of
known input devices. Output controllers of input-output controllers
230 could include controllers for any of a variety of known display
devices for presenting information to a user, whether a human or a
machine, whether local or remote. If one of these display devices
provides visual information, this information typically may be
logically and/or physically organized as an array of picture
elements, sometimes referred to as pixels. GUI controller 215 may
comprise any of a variety of known or future software programs for
providing graphical input and output interfaces between computer
100A and a user 201 (e.g., an experimenter wishing to use arrayer
120 to generate spotted arrays), and for processing inputs from
user 201 (hereafter sometimes referred to as user inputs or user
selections).
Arrayer Manager Application 290
[0053] Arrayer manager application 290 of the illustrated
implementation is a software application that controls functions of
arrayer 120 and processes data supplied by user 201. As more
particularly described with respect to certain implementations in
U.S. Provisional Pat. Application Serial No. 60/288,403,
incorporated by reference above, application 290, when executed in
coordination with processor 205, operating system 210, and/or GUI
controller 215, performs user interface functions, data processing
operations, and data transfer and storage operations. For example,
with respect to user interface functions, user 201 may employ one
or more of GUI's 282 to specify and describe particular clones and
their location in particular wells of particular well plates. Using
another of GUI's 282, user 201 may specify how spots of the clones
are to be arranged in arrays on one or more slides, as described in
greater detail below with respect to fields 304 and 306 of array
content file 292 shown in FIG. 3A. Yet another of GUI's 282 may be
used to operate arrayer 120, e.g., to initiate the spotting of a
number of slides without further user participation.
[0054] As will be evident to those skilled in the relevant art,
application 290 may be loaded into system memory 220 and/or memory
storage device 225 through an input device of devices 280.
Alternatively, application 290 may be implemented as executable
instructions stored in firmware. Executable code corresponding to
application 290 is referred to as arrayer manager application
executable 290' and is shown for convenience with respect to the
illustrated implementation as stored in system memory 220. However,
instructions and data including executable instructions of
application 290, and data used or generated by it, may be located
in or shifted among other memory devices, local or remote, as
convenient for data storage, data retrieval, and/or execution.
[0055] FIG. 3A is a graphical representation of illustrative data
records in one implementation of a data file generated by arrayer
manager application executable 290'. The data file in this
illustration, referred to as array content file 292, consists of
records 301, each one of which (i.e., records 301A through 301N for
any number of N records) corresponds to one of N spots, i.e.,
probes, that have been deposited, or are planned to be deposited,
on spotted arrays 121. For example, with reference to the graphical
representation of spotted arrays 121 shown in FIG. 3B, two arrays
121A and 121B (collectively, arrays 121) have been printed on
microscope slide substrate 333 by arrayer 120. Array 121A includes
probe 370A. It is assumed for purposes of illustration that data
relating to probe 370A is stored by executable 290' in probe record
301A. In this example, each of the records in file 292 includes the
following illustrative fields: probe identifier(s) 302, probe
x-coordinate identifier(s) 304, probe y-coordinate identifier(s)
306, probe data 308, probe data links 310, pin identifier 312, well
plate identifier 316, and user-supplied data 320.
[0056] The field in record 301A labeled probe identifier(s) 302A
thus, in this example, includes certain information related to the
identification of probe 370A. For instance, field 302A may include
a name for cDNA deposited by a pin of arrayer 120 in array 121A to
produce probe 370A. In various implementations, field 302A may
also, or in addition, include a nucleotide identifier and/or a gene
symbol that identifies probe 370A. Also, field 302A may include a
build or release number of a database so that the data source used
to develop the probe can be identified. As yet another example of
information that may be included in field 302A, a probe may be
identified as either an original or as a replicate. For instance,
for quality control or other reasons, probe 370B of array 121A may
be the same probe as probe 370A, or a number of such replicate
probes may be deposited. The designation of original or replicate
number assists in comparing results from probes that are based on
the same sample. As one of ordinary skill in the relevant art will
readily appreciate, all or some of this identifying data may be
stored as a single value in field 302A (such as, for example,
concatenating name, nucleotide identifier, etc.), in separate
fields (e.g., 302A', 302A", etc., not shown), in linked fields, and
so on as may be convenient for data storage and/or processing. The
other fields described below similarly are only representative of
many possible storage and data retrieval architectures.
[0057] Field 308A, labeled probe data in this example, may include
probe-related data such as the chromosome location of the gene or
EST represented by the probe, the band location on the chromosome,
a SNP or other type of marker that can identify the location on the
chromosome, and so on. Field 310A, labeled probe data links in this
example, similarly may include an accession number from GenBank, a
UniGene cluster number, and/or another identifier that facilitates
access to data related to probe 370A that is stored in a database.
This database may, but need not, be external to computer 100A and
accessed via network 125 and/or the Internet or other network.
Systems for providing access to such information are described, for
example, in U.S. Provisional Pat. Application, Serial No.
60/288,429, hereby incorporated herein by reference in its
entirety. Field 312A of this example identifies the pin on the
print head(s) that is used to deposit probe 370A onto the slide.
This information may be useful in comparing probes deposited with
the same pin to determine, for example, if the pin is defective.
Fields 314A and 316A contain information that respectively
identifies the well plate and particular well from which biological
fluid was taken to create probe 370A. Field 320A may contain a
variety of data supplied by user 201 such as the user's name, the
data of the experiment, and so on. It will be understood that there
are many other types of data relating to probe 370A that may be
stored, and that numerous alternative arrangements may be
implemented for storing them.
[0058] Fields 304A and 306A are used to identify the location of
probe 370A on the slide in x and y coordinates, respectively. It
will be understood that other coordinate systems (e.g., radial
system) could be used, and that the definition of the orientation
and zero points of the coordinate references of the present example
are illustrative only. In one implementation of the present
example, field 304A could include primary and secondary row
coordinates, and field 306A could include primary and secondary
column coordinates, that identify the position of probe 370A. For
instance, arrays 121A and 121B could be viewed as arranged in a
single primary column (disposed horizontally in FIG. 3B) in which
array 121A occupies the first primary row and array 121B occupies
the second primary row. Such an implementation may be said to
involve relative, rather than absolute, locations because locations
of probes are specified in relation to each other rather than in
relation to a reference point on the substrate. It may be
advantageous in some implementations to specify absolute, rather
than relative, locations. In one such implementation, orthogonal x
and y axes could be defmed in relation to the sides of the
microscope slide, such as x axis 392 and y axis 394 of the
illustrated example, with the 0,0 reference coordinates defined
with reference to a particular point on the slide. For instance,
some slides are manufactured with a frosted area, such as area 380
of this example, so that a user may more easily label or write on
the slide, or for other reasons. A particular point at a comer of
the frosted area could readily be defined as the reference
coordinate, or any of various other methods could be used to
specify a reference coordinate on, or spatially related to, a point
on the substrate.
Scanner 160A: Optics and Detectors
[0059] Any of a variety of conventional techniques, or ones to be
developed in the future, may be used to generate probe-target pairs
in probe arrays that may be detected using a scanner. As one
illustrative example that will be familiar to those of ordinary
skill in the relevant art, conventional fluidics stations,
hybridization chambers, and/or various manual techniques (as, for
example, generally and collectively represented by hybridization
process 122 in FIG. 1) may be used to apply one or more labeled
targets to spotted arrays on microscope slides. In a particular
implementation, for instance, sample of a first target may be
labeled with a first dye (an example of what may more generally be
referred to hereafter as an "emission label") that fluoresces at a
particular characteristic frequency, or narrow band of frequencies,
in response to an excitation source of a particular frequency. A
second target may be labeled with a second dye that fluoresces at a
different characteristic frequency. The excitation source for the
second dye may, but need not, have a different excitation frequency
than the source that excites the first dye, e.g., the excitation
sources could be the same, or different, lasers. The target samples
may be mixed and applied to the probes of spotted arrays on
microscope slides, and conditions may be created conducive to
hybridization reactions, all in accordance with known techniques.
In accordance with other techniques, such as typically are applied
with respect to Affymetrix.RTM. GeneChip.RTM. synthesized arrays,
samples of one labeled target are applied to one array and samples
of a second labeled target are applied to a second array having the
same probes as the first array. Hybridization techniques are
applied to both arrays. For example, synthesized arrays 134 of FIG.
1 may be illustratively assumed to be two GeneChip.RTM. synthesized
arrays that have been subject to hybridization processes with
respect to two different target samples, each labeled with
different fluorescent dyes. See, e.g., U.S. Pat. No. 6,114,122,
which is hereby incorporated by reference herein in its
entirety.
[0060] Many scanner designs may be used to provide excitation
signals to excite labels on targets or probes, and to detect the
emission signals from the excited labels. In references herein to
illustrative implementations, the term "excitation beam" may be
used to refer to light beams generated by lasers to provide the
excitation signal. However, excitation sources other than lasers
may be used in alternative implementations. Thus, the term
"excitation beam" is used broadly herein. The term "emission beam"
also is used broadly herein. As noted, a variety of conventional
scanners detect fluorescent or other emissions from labeled target
molecules or other material associated with biological probes.
Other conventional scanners detect transmitted, reflected,
refracted, or scattered radiation from such targets. These
processes are sometimes generally and collectively referred to
hereafter for convenience simply as involving the detection of
"emission beams." The signals detected from the emission beams are
generally referred to hereafter as "emission signals" or
"emissions," and these terms are intended to have a broad meaning
commensurate with that intended herein for the term "emission
beams."
[0061] Various detection schemes are employed depending on the type
of emissions and other factors. A typical scheme employs optical
and other elements to provide an excitation beam, such as from a
laser, and to selectively collect the emission beams. Also
generally included are various light-detector systems employing
photodiodes, charge-coupled devices, photomultiplier tubes, or
similar devices to register the collected emission beams. For
example, a scanning system for use with a fluorescently labeled
target is described in U.S. Pat. No. 5,143,854, hereby incorporated
by reference in its entirety for all purposes. Other scanners or
scanning systems are described in U.S. Pat. Nos. 5,578,832,
5,631,734, 5,834,758, 5,936,324, 5,981,956, 6,025,601, 6,141,096,
6,185,030, 6,201,639, 6,218,803, and 6,252,236; in PCT Application
PCT/US99/06097 (published as WO 99/47964); in U.S. patent
application, Ser. No. 09/681,819; and in U.S. Provisional Pat.
Application Serial No. 60/286,578, each of which also is hereby
incorporated herein by reference in its entirety for all
purposes.
[0062] FIG. 4 is a simplified graphical representation of selected
components of an illustrative type of scanner 160A suitable for
scanning hybridized spotted arrays 132A and 132B disposed on slide
333 (i.e., in this example, spotted arrays 121A and 121B,
respectively, after hybridization process 122). These illustrative
components, which will be understood to be non-limiting and not
exhaustive, are referred to collectively for convenience as scanner
optics and detectors 400. Scanner optics and detectors 400 include
excitation sources 420A and 420B (collectively referred to as
excitation sources 420). Any number of one or more excitation
sources 420 may be used in alternative embodiments. In the present
example, sources 420 are lasers; in particular, source 420A is a
diode laser producing red laser light having a wavelength of 635
nanometers and, source 420B is a doubled YAG laser producing green
laser light having a wavelength of 532 nanometers. Further
references herein to sources 420 generally will assume for
illustrative purposes that they are lasers, but, as noted, other
types of sources, e.g., x-ray sources, may be used in other
implementations.
[0063] Sources 120A and 120B may alternate in generating their
respective excitation beams 435A and 435B between successive scans,
groups of successive scans, or between full scans of an array.
Alternatively, both of sources 120 may be operational at the same
time. For clarity, excitation beams 435A and 435B are shown as
distinct from each other in FIG. 4. However, in practice, turning
mirror 424 and/or other optical elements (not shown) typically are
adjusted to provide that these beams follow the same path.
[0064] Scanner optics and detectors 400 also includes excitation
filters 425A and 425B that optically filter beams from excitation
sources 420A and 420B, respectively. The filtered excitation beams
from sources 420A and 420B may be combined in accordance with any
of a variety of known techniques. For example, one or more mirrors,
such as turning mirror 424, may be used to direct filtered beam
from source 420A through beam combiner 430. The filtered beam from
source 420B is directed at an angle incident upon beam combiner 430
such that the beams combine in accordance with optical properties
techniques well known to those of ordinary skill in the relevant
art. Most of combined excitation beams 435 are reflected by
dichroic mirror 436 and thence directed to periscope mirror 438 of
the illustrative example. However, dichroic mirror 436 has
characteristics selected so that portions of beams 435A and 435B,
referred to respectively as partial excitation beams 437A and 437B
and collectively as beams 437, pass through it so that they may be
detected by excitation detector 410, thereby producing excitation
signal 494.
[0065] In the illustrated example, excitation beams 435 are
directed via periscope mirror 438 and arm end turning mirror 442 to
an objective lens 445. As shown in FIGS. 5A and 5B, lens 445 in the
illustrated implementation is a small, light-weight lens located on
the end of an arm that is driven by a galvanometer around an axis
perpendicular to the plane represented by galvo rotation 449 shown
in FIG. 4. Objective lens 445 thus, in the present example, moves
in arcs over hybridized spotted arrays 132 disposed on slide 333.
Flourophores in hybridized probe-target pairs of arrays 132 that
have been excited by beams 435 emit emission beams 452 (beam 452A
in response to excitation beam 435A, and beam 452B in response to
excitation beam 435B) at characteristic wavelengths in accordance
with well-known principles. Emission beams 452 in the illustrated
example follows the reverse path as described with respect to
excitation beams 435 until reaching dichroic mirror 436. In
accordance with well-known techniques and principles, the
characteristics of mirror 436 are selected so that beams 452 (or
portions of them) pass through the mirror rather than being
reflected.
[0066] In the illustrated implementation, filter wheel 460 is
provided to filter out spectral components of emission beams 452
that are outside of the emission band of the fluorophore, thereby
providing filtered beams 454. The emission band is determined by
the characteristic emission frequencies of those fluorophores that
are responsive to the frequencies of excitation beams 435. In
accordance with techniques well known to those of ordinary skill in
the relevant arts, including that of confocal microscopy, filtered
beams 454 may be focused by various optical elements such as lens
465 and also passed through illustrative pinhole 467 or other
element to limit the depth of field, and thence impinges upon
emission detector 415.
[0067] Emission detector 415 may be a silicon detector for
providing an electrical signal representative of detected light, or
it may be a photodiode, a charge-coupled device, a photomultiplier
tube, or any other detection device that is now available or that
may be developed in the future for providing a signal indicative of
detected light. For convenience of illustration, detector 415 will
hereafter be assumed to be a photomultiplier tube (PMT). Detector
415 thus generates emission signal 492 that represents numbers of
photons detected from filtered emission beam 454.
[0068] FIG. 5A is a perspective view of a simplified representation
of the scanning arm portion of'scanner optics and detectors 400.
Arm 500 moves in arcs around axis 510, which is perpendicular to
the plane of galvo rotation 449. A position transducer 515 is
associated with galvanometer 515 that, in the illustrated
implementation, moves arm 500 in bi-directional arcs. Transducer
515, in accordance with any of a variety of known techniques,
provides an electrical signal indicative of the radial position of
arm 500. Certain non-limiting implementations of position
transducers for galvanometer-driven scanners are described in U.S.
Pat. No. 6,218,803, which is hereby incorporated by reference in
its entirety for all purposes. The signal from transducer 515 is
provided in the illustrated implementation to user computer 100B so
that clock pulses may be provided for digital sampling of emission
signal 492 when arm 500 is in certain positions along its scanning
arc.
[0069] Ann 500 is shown in alternative positions 500' and 500" as
it moves back and forth in scanning arcs about axis 510. Excitation
beams 435 pass through objective lens 445 on the end of arm 500 and
excite fluorophore labels on targets hybridized to certain of
probes 370 in arrays 132 disposed on slide 333, as described above.
The arcuate path of excitation beams 435 is schematically shown for
illustrative purposes as path 550. Emission beams 452 pass up
through objective lens 445 as noted above. Slide 333 of this
example is disposed on translation stage 542 that is moved in what
is referred to herein as the "y" direction 544 so that arcuate path
550 repeatedly crosses the plane of arrays 132.
[0070] FIG. 5B is a top planar view of arm 500 with objective lens
445 scanning arrays 132 as translation stage 542 is moved under
path 550. As shown in FIG. 5B, arcuate path 550 of this example is
such that arm 500 has a radial displacement of .theta. in each
direction from an axis parallel to direction 544. What is referred
to herein as the "x" direction, perpendicular to y-direction 544,
is shown in FIG. 5B as direction 543. Further details of confocal,
galvanometer-driven, arcuate, laser scanning instruments suitable
for detecting fluorescent emissions are provided in PCT Application
PCT/US99/06097 (published as WO99/47964) and in U.S. Pat. Nos.
6,185,030 and 6,201,639, all of which have been incorporated by
reference above. It will be understood that although a
galvanometer-driven, arcuate, scanner is described in this
illustrative implementation, many other designs are possible, such
as the voicecoil-driven scanner described in U.S. patent
application, Ser. No. 09/383,986, hereby incorporated herein by
reference in its entirety for all purposes.
[0071] FIG. 6A is a simplified graphical representation of
illustrative probe 370A as it is scanned by scanner 160A. It is
assumed for illustrative purposes that probe 370A has hybridized
with a fluorescently labeled target. Although FIG. 6A shows probe
370A in idealized form, i.e. a perfect circle, it will be
understood that many shapes, including irregular shapes, are
possible.
[0072] In the manner described above, objective lens 445 scans over
probe 370A (and other probes of arrays 132) in bidirectional arcs.
An illustrative scan 620 is shown in FIG. 6A, which is not
necessarily drawn to scale; e.g., the ratio of the radius of the
arc of scan 620 to the radius of probe 370A is illustrative only.
As also noted, probe 370A moves under objective lens 445 carried by
translation stage 542 in y-direction 544. In particular, in the
illustrated implementation, arm 500 scans in an arc in one
direction, shown as left-to-right scan 620 in FIG. 6A. Translation
stage 542 is then moved incrementally by a stepping motor (not
shown) in y-direction 544 and arm 500 then scans back in the
opposite direction, shown as right-to-left arcuate scan 622.
Translation stage 542 is again moved in direction 544, and so on in
scan-step-scan-step sequences. The distance between scans 620 and
622 thus corresponds to the distance that translation stage 542 is
moved in each increment, although it will be understood that the
distance shown in FIG. 6A is not necessarily to scale and is
illustrative only. It will be understood that any other combination
of scanning and stepping is possible in alternative
implementations, and that scanning and moving of translation stage
542 may occur at the same or at overlapping times in some
implementations. Translation stage 542 need not be stepped in some
implementations, but may, for example, be moved continuously.
[0073] FIG. 6B is a plot having a pixel clock axis 630 showing when
clock pulses 632 occur. Clock pulses 632 may be generated by a
pixel clock of scanner 160A (e.g., complex programmable logic
device 830, described below) or, alternatively, they may be
generated by software executing in computer 100B(e.g., executable
790', described below). Axis 630 in the illustrated implementation
is a spatial axis; that is, each of clock pulses 632 occurs in
reference to the radial location of arm 500 during each scan, as
described in greater detail below. Thus, with reference to the
position of translation stage 542 indicated by scan 620, a clock
pulse 632A occurs prior to arm 500 passing over probe 370A from the
left as shown in FIGS. 6A and 6B. (For sake of clarity of
illustration only, vertical dotted lines are provided between FIGS.
6A and 6B, and between FIGS. 6B and 6C, to illustrate the alignment
of these figures.) As another example, clock pulse 632C occurs with
respect to scan 620 when arm 500 has just passed over portions of
probe 370A indicated by pixel areas 610A and 610B. These areas are
referred to as pixel areas because a digital value is assigned to
each such area in the illustrated implementation based on the
strength of a processed emission signal associated with that area.
In accordance with known techniques, clock pulses 632 enable the
digital sampling of the processed emission signal.
[0074] As noted, clock pulses 632 are spatially rather than
temporally determined in the illustrated implementation. Moreover,
in some aspects of the illustrated implementation, galvanometer 516
is driven by a control signal provided by user computer 100B such
that the velocity of arm 500 in x-direction 444 is constant in time
during those times when arm 500 is over probe 370A (and, typically,
over other of probes 370 of arrays 132 as they are scanned). That
is, dx/dt is a constant (and thus the angular velocity varies) over
the probe-scanning portions of each arc and, in particular, it is a
constant during the times when clock pulses are generated to enable
digital sampling. As is evident, dx/dt must be reduced to zero
between each successive scan, but this deceleration and reversal of
direction takes place after arm 500 has passed over probe 370A (or,
more generally, array 132A or 132B). The design and implementation
of a galvanometer control signal to provide constant dx/dt are
readily accomplished by those of ordinary skill in the relevant
art.
[0075] Thus, the approximate sampling rate may readily be
calculated based on the desired scanning speed (dx/dt) and desired
pixel resolution. To provide an illustrative example, a spot
deposited by an Affymetrix.RTM. 417.TM. or 427.TM. Arrayer
typically has a diameter of approximately 150 to 200 microns.
Spotted arrays made using these instruments typically may be
deposited over a surface having a width of about 22 millimeters on
a microscope slide that is 25 millimeters wide. In order to achieve
pixel resolution of about 10 microns, a sampling rate of about 160
kHz is sufficient for scanning speeds typical for scanners used
with respect to these probe arrays, such as the Affymetrix.RTM.
428.TM. scanner. Other sampling rates, readily determined by those
of ordinary skill, may be used in other applications in which, for
example, different scanning speeds are used and/or different pixel
resolutions are desired. The desired pixel resolution typically is
a function of the size of the probe features, the possibility of
variation in detected fluorescence within a probe feature, and
other factors.
[0076] FIG. 6C shows digital values representative of emission
signal 492 as sampled at (and/or collected for an adjoining period
before) points on scans 620 and 622 represented by constant radial
position lines 625A-K (collectively referred to as radial position
lines 625). The voltages sampled during scan 620 are shown as dots,
while the voltages sampled during scan 622 are shown as x's. The
determination of when to initiate pixel clock signals may be made
using position transducer 515, as described in greater detail in
U.S. Provisional Patent Application Serial No. 60/286,578,
incorporated by reference above. Thus, for example, voltage 650C of
FIG. 6C is representative of emission signal 492 based on sampling
enabled by a pixel clock pulse at point 632C on axis 630 that is
triggered when arm 500 is at radial position 625C during scan 620.
After translation stage 542 has been incremented, voltage 652C is
sampled during scan 622 at the same radial position, shown as
radial position 625C".
User Computer 100B
[0077] As shown in FIG. 1 and noted above, scanner 160B operates in
the illustrated implementation under computer control, e.g., under
the control of user computer 100B, as shown in greater detail in
FIG. 7. Although computer 100B is shown in FIGS. 1 and 7 for
clarity as being directly coupled to scanner 160A, it may
alternatively be coupled to scanner 160A over a local-area,
wide-area, or other network, including an intranet and/or the
Internet. Computer 100B may be a personal computer, a workstation,
a server, or any other type of computing platform now available or
that may be developed in the future. Typically, computer 100B
includes known components such as processor (e.g., CPU) 705,
operating system 710, system memory 720, memory storage devices
725, GUI controller 715, and input-output controllers 730, all of
which typically communicate in accordance with known techniques
such as via system bus 704. It will be understood by those skilled
in the relevant art that there are many possible configurations of
the components of computer 100B and that some components that may
typically be included in computer 100B are not shown, such as cache
memory, a data backup unit, and many other devices.
[0078] Input-output controllers 730 could include any of a variety
of known devices for accepting and processing information from a
user, whether a human or a machine, whether local or remote. Such
devices include, for example, modem cards, network interface cards,
sound cards, or other types of controllers for any of a variety of
known input devices. Output controllers of input-output controllers
730 could include controllers for any of a variety of known display
devices for presenting information to a user, whether a human or a
machine, whether local or remote. If one of these display devices
provides visual information, this information typically may be
logically and/or physically organized as an array of picture
elements, sometimes referred to as pixels. Graphical user interface
(GUI) controller 715 may comprise any of a variety of known or
future software programs for providing graphical input and output
interfaces between computer 100B and a user 701 (e.g., an
experimenter wishing to use scanner 160A to acquire and analyze
information from spotted arrays), and for processing inputs from
user 701 (hereafter sometimes referred to as user inputs or user
selections). To avoid confusion, references hereafter to a "GUI"
generally are directed to one or more graphical user interfaces
displayed on a display device of devices 780 to user 701, such as
GUI 782A of FIGS. 8 and 9, described below. To be distinguished are
references to a "GUI controller," such as GUI controller 715, that
operates to display the GUI's to user 701 and to process input
information provided by user 701 through the GUI's. As is well
known in the relevant art, a user may provide input information
using a GUI by selecting, pointing, typing, speaking, and/or
otherwise operating, or providing information into, one or more
input devices of devices 780 in a known manner.
[0079] Computer 100B may optionally include process controller 740
that may, for example, be any of a variety of PC-based digital
signal processing (DSP) controller boards, such as the M44 DSP
Board made by Innovative Integration of Simi Valley, Calif. More
generally, controller 740 may be implemented in software, hardware
or firmware, or any combination thereof.
Scanner Control and Analysis Application 790
[0080] Scanner control application 790 of the illustrated
implementation is a software application that controls functions of
scanner 160A. In addition, when executed in coordination with
processor 705, operating system 710, GUI controller 715, and/or
process controller 740, application 790 performs user interface
functions, data and image processing operations, and data transfer
and storage operations related to data provided by or to scanner
160A and/or user 701, as described in greater detail below.
Affymetrix.RTM. Jaguar.TM. software, available from Affymetrix,
Inc., is a commercial product that, in some implementations,
includes various aspects of application 790.
[0081] As more particularly shown in FIG. 8, scanner control
application 790 in the illustrated implementation includes a GUI
manager 810 that, in accordance with known techniques, receives and
processes user selections of windows for display and user
selections of features within one or more of the displayed windows.
GUI manager 810 also builds and displays, in accordance with known
techniques, the windows, features, and selections according to
templates and other stored data as well as user data 794, array
data 792, image data 798, and image analysis data 799. Also
included in application 790 is image processor 820 that receives
image data 798 from scanner 160A. In particular, in the
illustrative implementation image analyzer 852 of processor 820
receives data 798 and analyzes it to provide image analysis data
799. Data 799 is stored by storer 855 in system memory 720 and also
provided to GUI manager 810 for inclusion in GUI 782A. Similarly,
image data 798 may be provided to GUI manager 810 for inclusion in
GUI 782A.
[0082] For convenience of further description, it is illustratively
assumed that user 701 indicates that three openable windows are to
be displayed, as represented by illustrative GUI 782A of FIG. 8 and
shown in greater detail in FIG. 9. It will be understood that GUI
782A of FIG. 9 is illustrative only, and that numerous variations,
alternative, and/or rearrangements of the information and features
described herein with respect to GUI 782A may be provided in other
implementations.
[0083] It will be illustratively assumed that user 701 selects
three openable windows to be displayed in GUI 782A. This selection
may be accomplished in accordance with a variety of known
techniques, such as by selecting the windows from a pull down menu,
e.g., from "View" menu 960 of FIG. 9. As shown in FIG. 9, GUI 782A
of this example thus includes first window 905 that includes a
plurality of image features, referred to for convenience as spots
951, such as spots 951A-D. Spots 951 of this implementation may be
considered to be pseudo-images of probes in one or more spotted
arrays. Thus, for example, a visual characteristic of image feature
951A represents a hybridization reaction associated with a probe of
a spotted array arranged in the upper left quadrant of first window
905. Spots 951B and 951C are associated with another spotted array,
the pseudo-image of which is arranged in the upper right quadrant.
Similarly, spot 951D is associated with a third spotted array, the
pseudo-image of which is arranged in the lower right quadrant of
first window 905. In this example, the visual characteristic may be
the gray-scale intensity of spots 951. Many of spots 951 appear of
equal intensity in this example, but it will be understood that
this is a simplification for convenience of illustration only. In
general, the intensity or other visual or other characteristic of
spots 951 may vary to represent a degree, efficiency, or intensity
of hybridization of a probe-target pair.
[0084] It is also illustratively assumed with respect to GUI 782A
of FIG. 9 that user 701 has selected to display, i.e., open, second
openable window 907 that, in this illustrative implementation, is a
scatter plot or graph. Window 907 includes a plurality of data
features 952, such as represented in this example by dots 952
including dots 952A-D. The placement of each of dots 952 in
relation to horizontal axis 956 and vertical axis 957 of the
scatter plot indicates, in this example, the intensity of
hybridization of a probe in relation to emissions from a first dye
attached, for example, to a first target and emissions from a
second dye attached to a second target. For instance, the placement
of dot 952A in relation to axis 956 indicates the intensity of an
emission signal due to the probe associated with dot 952A
hybridizing to a first target labeled with the first dye, and the
placement of dot 952A in relation to axis 957 indicates the
intensity of an emission signal due to the same probe hybridizing
to a second target labeled with the second dye. In this
implementation, the intensities of the emission signals, and thus
the plot of window 907, are provided in log scale. However, other
scales, such as linear scale, may be employed in other
implementations.
[0085] In the illustrative implementation, second window 907 is
displayed by overlaying it on top of first window 905. However, in
alternative implementations, the windows may be displayed without
overlapping or overlaying, in accordance with known techniques.
Also in accordance with known techniques, any of the windows may be
resized, moved, or rearranged by user 701.
[0086] It is further assumed that user 701 has selected to display
third window 906 that, in this implementation, is a spreadsheet.
The spreadsheet includes a plurality of descriptive features, i.e.,
rows in this example. Thus, for instance, row 953A is shown that
provides information about a probe in the scanned probe array. The
descriptive elements in this row, each arranged in a separate
column, include, for example, a "Row" element having a value "1"
and a "Col" element having a value "8."
[0087] It is assumed for illustrative purposes that user 701
selects row 953A. GUI manager 810 causes row 953A to be highlighted
in accordance with known techniques. GUI manager 810 has populated
row 953A (and the other displayed rows of the spreadsheet) with
information available to manager 810 from array data 792, user data
794, image data 798 and/or image analysis data 799. For example, in
the illustrated example, the values "1" in the "Row" column and "8"
in the "Col" column indicate that the probe associated with row
953A is located in the first row and eighth column of the probe
array. Other of array data 792, e.g., primary rows and columns as
described above, may be provided in alternative examples to
indicate which of the arrays shown in window 905 constitute the
array in which the probe corresponding to row 953A is located. As
additional examples, the value of the descriptive element of row
953A arranged under the column labeled "Cy3 Signal" indicates an
intensity of the emission signal from the dye Cy3 detected by
scanner 160A by scanning the probe associated with row 953A.
[0088] In accordance with some implementations of the present
invention, GUI manager 810 automatically highlights the features of
window 905 and window 907 corresponding to the user-selected and
highlighted feature of window 906. Thus, as shown in GUI 782A of
FIG. 9, GUI manager 810 causes spot 951A of window 905 to be
highlighted (i.e., in this example a white circle highlights the
spot's boundaries) and causes dot 952A of window 907 to be
highlighted (i.e., a circle is drawn around it in this example). In
addition, in this implementation textual element 955 is provided at
the bottom of window 907 that shows intensity information related
to the highlighted dot 952A. The preceding illustrative description
could also have assumed that user 701 selected spot 951A, thus
causing GUI manager 810 to highlight row 953A and dot 952A, or that
user 701 selected dot 952A, causing GUI manager 810 to highlight
row 953A and spot 951A. In any of these cases, dot 952A, textual
element 955, spot 951A, and row 953A all provide user 701 with
easily accessible and correlated information regarding a common
probe. Advantageously, this information may be displayed to user
701 in simultaneously displayed windows on GUI 782A. In other
examples, user 701 may have selected any two of the three
illustrative windows described above.
[0089] Additional embodiments are described in the copending PCT
Application PCT/IUS01/______ entitled "System Method and Software
Product for Controlling Biological Microarray Scanner" filed on
Aug. 22, 2001, which is incorporated by reference as if fully
provided herein.
[0090] Having described various embodiments and implementations of
the present invention, it should be apparent to those skilled in
the relevant art that the foregoing is illustrative only and not
limiting, having been presented by way of example only. Many other
schemes for distributing functions among the various functional
elements of the illustrated embodiment are possible in accordance
with the present invention. The functions of any element may be
carried out in various ways in alternative embodiments. Also, the
functions of several elements may, in alternative embodiments, be
carried out by fewer, or a single, element.
[0091] For example, arrayer manager application 290 is described as
executing on computer 100A that controls arrayer 120, and scanner
control application 390 is described as executing on computer 100B
that control scanner 160A. However, aspects of the invention need
not be divided into these distinct functional elements. Rather, for
example, applications 290 and 390 could be executed on a same
computer that may, for example, control both arrayer 120 and
scanner 160A. Moreover, applications 290 and 390 may be part of a
same computer program product irrespective of whether they are
executed on a same, or different, computers.
[0092] In addition, it will be understood by those skilled in the
relevant art that control and data flows between and among
functional elements of the invention and various data structures
may vary in many ways from the control and data flows described
above. More particularly, intermediary functional elements (not
shown) may direct control or data flows, and the functions of
various elements may be combined, divided, or otherwise rearranged
to allow parallel processing or for other reasons. Also,
intermediate data structures or files may be used, various
described data structures or files may be combined, the sequencing
of functions or portions of functions generally may be altered, and
so on. Numerous other embodiments, and modifications thereof, are
contemplated as falling within the scope of the present invention
as defined by appended claims and equivalents thereto.
Copyright Statement
[0093] A portion of the disclosure of this patent document contains
material that is subject to copyright protection. The copyright
owner has no objection to the facsimile reproduction by anyone of
the patent document or the patent disclosure as it appears in any
Patent Office patent file or records, but otherwise reserves all
copyright rights whatsoever.
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