WO2001065349A1

WO2001065349A1 - Computer user interface for visualizing assay results

Info

Publication number: WO2001065349A1
Application number: PCT/US2001/006784
Authority: WO
Inventors: Marc E. Navre
Original assignee: Smithkline Beecham Corporation
Priority date: 2000-03-01
Filing date: 2001-03-01
Publication date: 2001-09-07
Also published as: AU2001245399A1

Abstract

A computer system and GUI (100) are provided to visually represent quantitative data (103). Data is displayed in the form of a two-dimensional, graphical object (101) that allows the user to quickly interpret multi-dimensional data upon visual inspection of the object, typically by representing quantitative aspects of the data by gradations of color. The quantitative results of the assays are represented as gradations of color or gray in the sub-areas (112). The user can manipulate the system and the graphical object to display the information in different format (111).

Description

COMPUTER USER INTERFACE FOR VISUALIZING ASSAY RESULTS

FIELD OF THE INVENTION

The present invention relates generally to user interface software running on computers or computer systems. More specifically, the invention relates to user interface systems and methods for visually representing quantitative data.

BACKGROUND OF THE INVENTION

In computer applications, there are numerous ways to present user information. Graphical user interfaces (GUIs) on computer systems allow easy use of windows, control icons, etc., to display information to the user. The data displayed in a window may be of different types. Some may be graphical, such as icons or pictures, or textual, such as a word processing document, or a combination of both. Computer applications with GUIs can be of use in scientific studies where the user wishes to analyze, organize, and present empirical data. Generally, such data is stored in a spreadsheet, data file or database, and accessed using a query system such as SQL. The computer application will then access the data and present it in the form of numerical tables, bar graphs or other common means of data presentation.

While providing a basic level of organization to quantitative data, such generic formats do not provide effective means of visually representing the data, particularly when the number of data samples is large and the data is itself multi-dimensional (where two dimensions cannot readily convey the complexity of the data). One of the major challenges in creating useful scientific data computer applications, therefore, is to develop visual representation systems that can convey the complex meaning of large amounts of multi-dimensional data. Such a computer application would present the data in a form that the user can intuitively understand and whereby he can quickly apprehend key aspects of the data by visual inspection.

Biochemical assays present a particularly difficult challenge for visual data representation. Such assays are generally run on multi-well microtitre plates, where each well contains a test agent (generally a compound, drug or biological material) that is being tested or screened, i.e., assayed, for a particular characteristic. At a time when throughput for biochemical assays was low, when only a few, or perhaps only one, plate of 36 or 48 wells could be run in a day, a biochemist could perhaps interpret the data in a reasonable amount of time from generic display formats that were not specially designed for this data, e.g., simple tables or bar graphs. Today, however, biochemistry assays are run on industry standard plates that typically have 96, 384, 864 or 1536 wells, and high- throughput automation allows scientists to rapidly and continually generate such plates. The generic data presentation formats of the current art do not provide effective means of presenting the data from such assays, a shortcoming that has and will become more and more problematic as increasingly rapid high-throughput techniques are introduced.

In view of the foregoing, a graphics user interface with effective visual presentation formats that are specifically designed to present multi-dimensional data from multi-test assays would be highly beneficial.

SUMMARY OF THE INVENTION

The present invention addresses this need by providing a computer user application interface that includes a two-dimensional graphical object that presents, multi-dimensional data in an effective and clear manner. The computer application accepts data from a database, spreadsheet, user input or by any other common means.

In a preferred embodiment, the graphical object displays a number of areas, each area representing a different test agent or candidate, and each area presenting the results from at least two assays run against the test agent. The areas may be circles or rectangles, for example. The test areas are divided into a number of sub-areas, each representing a single assay result on the test agent. The quantitative results of the assays are represented as color-level or gray-level gradations in the sub-areas. If color is used, the colors in the sub-areas may be all different, all the same, or may be some combination thereof. The user can manipulate the system and the graphical object to display the information in different formats.

One aspect of the invention pertains to computer systems capable of visually displaying multi-dimensional quantitative data from a plurality of assays conducted on source arrays. The computer system may be characterized by the following features: a graphical user interface running on hardware including at least one or more processors, one or more user input devices, and a display capable of visually displaying the multidimensional data. The graphical user interface provides a two-dimensional graphical object that represents the multi-dimensional data by a plurality of areas, with each area representing multiple assay results of a particular test agent. For example, a test area A may present data for a test agent X, including anti-microbial assay results, solubility assay results, and toxicity assay results. Each such area includes at least two sub-areas of colors or levels of gray, with each sub-area representing a particular assay conducted on the same test agent associated with the area. Within each sub-area, gradations of the colors or levels of gray are used to convey quantitative aspects of each assay.

Typically, the source arrays are testing media (e.g., microtitre plates) having discrete regions (e.g., wells) for separate biological, biochemical, or chemical tests. The areas may be presented as rectangles or circles, for example. The sub-areas may be presented as bars, concentric rings, pie sectors of a circle, and the like. To facilitate visual interpretation of the displayed assay results, some colors may be graded more darkly to represent larger quantitative results and other colors may be graded more darkly to represent smaller quantitative results. Still further, some assay results or test agents may be visually emphasized by highlighting or otherwise marking specific sub- areas or areas. Other assay results or test agents may be visually deemphasized. The highlighting may be triggered by certain criteria such as threshold assay values or combinations thereof.

Another aspect of the invention pertains to computer systems as described above, wherein the graphical user interface provides a two-dimensional graphical object that represents multi-dimensional data via a plurality of areas that are displayed in an arrangement that conveys spatial information from such source arrays. Each source array has a plurality of test regions, and those test regions are represented, along with their relative spatial location with respect to each other, by the areas of the graphical object. For example, if the source array is a 96-well (8 x 12) microtitre plate, then the graphical object also has 96 areas, displayed in the same spatial arrangement as the test regions/wells of the microtitre plate. Typically, each area also includes at least two sub- areas of colors or levels of gray, with each sub-area representing a particular assay conducted on the same test agent associated with the area. The shape of the areas and sub-areas, as well as their coloring, are typically as described above. Another aspect of the invention pertains to computer systems as described above, wherein the user chooses the precise visual format of the two-dimensional graphical object used to represent the multi-dimensional data, via input from a graphical user interface element or elements. The types of source arrays, as well as the visual format of the graphical object, including its areas and sub-areas, is typically as described above.

Another aspect of the invention pertains to computer-implemented methods for implementing the graphic user interface and two-dimensional graphical object of the invention. The method of the invention can be implemented on any of the computer systems described above. The method includes providing a two-dimensional graphical object that represents the multi-dimensional data via a plurality of areas, with each area representing multiple assay results of a particular test agent. Each such area includes at least two sub-areas of different colors or levels of gray, with each sub-area quantitatively representing a particular assay by gradations of the colors or levels of gray. The types of source arrays, as well as the visual format and graphical elements of the method are as described in the computer system implementations above.

Another method aspect of the invention provides a two-dimensional graphical object that represents multi-dimensional data via a plurality of areas that are displayed in an arrangement that conveys spatial information from such source arrays. Each source array has a plurality of test regions, and those test regions are represented, along with their relative spatial location with respect to each other, by the areas of the graphical object. Another method aspect of the invention provides for the user choosing the precise visual format of the two-dimensional graphical object used to represent the multi-dimensional data, via input from a graphical user interface element or elements.

Another aspect of the invention pertains to computer-program products including a machine-readable medium on which is provided program instructions for implementing one or more of the computer system user interfaces or methods described herein. Any of the computer system user interfaces or methods of the invention may be represented as program instructions that can be provided on such computer-readable media.

These and other features of the present invention will be described in more detail below in the detailed description of the invention and in conjunction with the following figures. BRIEF DESCPJP TION OF THE DRAWINGS

The file of this patent contains at least one drawing executed in color. Copies of this patent with color drawmgs will be provided by the Patent and Trademark Office upon request and payment of the necessary fee. The drawings executed in color are FIGs. 1-14 listed below.

The present invention is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawmgs and in which like reference numerals refer to similar elements and in which:

FIG. 1 illustrates a graphical user interface with a display window and a three assay, 96-well data plate represented as the two-dimensional graphical object in "bulls- eye" mode.

FIG. 2 illustrates the same data plate of FIG. 1 in "pie" mode.

FIG. 3 illustrates the same data plate of FIG. 1 in "bar" mode.

FIG. 4 illustrates the "display mode" pull-down menu and example modes that can be selected from it.

FIG. 5 illustrates the same data plate of FIG. 1 in "vertical bar" mode.

FIG. 6 illustrates the same data plate of FIG.l in "bulls-eye+1" mode.

FIG. 7 illustrates the same data plate of FIG.1 in "pie+1" mode.

FIG. 8 illustrates the "options" dialog window presented when an options button is clicked.

FIG. 9 illustrates some of the pull-down menus available to the user.

FIG. 10 illustrates the "set criteria" dialog window presented when the user makes a selection from the "edit criteria" pull-down menu.

FIG. 11 illustrates the two-dimensional graphical object with highlighted areas that meet a criterion setting. FIG. 12 illustrates the two-dimensional graphical object with hidden areas that meet the same criterion setting of FIG. 11.

FIG. 13 illustrates how the present invention facilitates analysis of multidimensional quantitative data, in this case, a two-assay, 864-well data plate.

FIG. 14 illustrates how the two-dimensional graphical object of the present invention can elucidate structural activity relationships in a chemical combinatorial library.

FIG. 15 is a flowchart illustrating a typical process flow of the current invention for displaying a two-dimensional graphical object.

FIGs. 16A and 16B illustrate a computer system suitable for implementing embodiments of the present invention.

DETAILED DESCRIPTION

In the following detailed description of the present invention, numerous specific embodiments are set forth in order to provide a thorough understanding of the invention. However, as will be apparent to those skilled in the art, the present invention may be practiced without these specific details or by using alternate elements or processes. In other instances well known processes, procedures, components, and circuits have not been described in detail so as not to unnecessarily obscure aspects of the present invention.

A "source array" as referred to herein pertains to the substrate or associated spatial arrangement of tests employed in any multi-test assay. A source array typically includes some sort of substrate, such as glass, plastic or a cell culture medium, on which to perform the tests. In some cases, the source array is designed to keep test agents in physically separate regions, such as reaction wells. An example of a typical source array is a microtitre plate that is typically used to perform biological, chemical or biochemical assays. A microtitre plate is composed of a plurality of wells typically in a rectangular arrangement. A user places a different test agent, typically a compound, biological agent or some other substance to be assayed, in each well. If the user is assaying three different properties, he will typically use three separate plates, each identical in terms of the test agents (and their well locations on the plates), but different in terms of the assays run on them. Other examples of source arrays include dense arrays of polynucleotides

(or other polymers) such as the GeneChip™ by Affymetrix of Santa Clara, California, membrane-based arrays, and the like.

An "assay" as referred to in this invention is an experimental test. Assays are generally run on test agents to screen for desirable properties. Assays are often, but not exclusively, biological, chemical or biochemical in nature, and the borderlines between such categories is not at all sharp. An example of a biological assay is the screening of bacteria cultures or cell lines for antibiotic resistance. An example of a chemical assay is the screening of a chemical library for catalytic activity, solubility, or some other chemical property. An example of biochemical assay is the screening of a combinatorial drug library for toxicity or pathway inhibition. Of interest in the context of the present invention are assays employing source arrays as described above. Importantly, such assays provide test data for multiple tests conducted in parallel. A "graphical object" of this invention generally presents quantitative results from two or more assays conducted on a single set of test agents (e.g., A library of potentially bioactive compounds). The object forms at least part of a graphical user interface running a computer system and is presented to a user by some sort of a display mechanism. The graphical object may present assay data in any of a number of formats. Typically, each individual "area" of the graphical object represent the results from two or more assays run on a "test agent" located on a source array such as a microtitre plate. As described more fully below, these areas are graphical display elements that reside within bounded regions separated from one another in a manner that corresponds to the arrangement of the test agents on a source array. Each area contains within its bounded region two or more sub-areas, each of which represents the results of a single assay. For example, if compound X is assayed for anti-bacterial activity and toxicity to human liver cells, a graphical element or "area" corresponding to compound X will include at least two sub-areas, one presenting the results of the anti-bacterial assay and the other presenting the results of the liver cell toxicity assay.

The graphical object may be presented on a graphical user interface as a single window or a collection of windows, for example. In preferred embodiments, illustrated in more detail herein, the color, layout, division of areas, and other display parameters of the graphical object can be adjusted by a collection of associated graphical interface user tools or controls.

An "area" of this invention generally presents the quantitative results from the assays being represented on a single test agent (e.g., a candidate compound being assayed for desired properties). Thus, just as the "source arrays" consist of a plurality of test agents the graphical object consists of a plurality of "areas" which each represent one of the agents. The areas of the graphical object are typically placed in an arrangement that mimics the source arrays from which the quantitative data derives, or at least placed in an arrangement which preserves the information about the relative spatial location of the test agents with respect to each other. The areas typically are rectangular or circular in shape, and consist of sub-areas.

A "sub-area" of this invention generally presents the quantitative results from just one assay on a single test agent, (e.g., Only the anti-bacterial activity of compound X). Each sub-area, taken alone, represents the result from one assay on one test agent. All of the sub-areas in an area, taken together, represent the results of all the assays on that one test agent. Thus the test agent "area" consists of assay "sub-areas" corresponding to individual assays. In one-preferred embodiment, the sub-areas are horizontal or vertical bars within a rectangular area. In another preferred embodiment, the sub-areas are circular "pie" sectors within a circular area, h another preferred embodiment, the sub- areas are circular "pie" sectors that make up a circle, except for one sub-area, which is a background sub-area that fills in the remainder of the area.

Each sub-area conveys its corresponding quantitative result through a gradation of color or gray. Typically, all the sub-areas that correspond to one assay, regardless of the area or test agent, are of the same color, which differs from the colors that correspond to different assays. Gradations of color may increase or decrease in relation to the quantitative result, as chosen by the user. A certain color gradation may correspond to a certain threshold (e.g., No color/result will be shown until a certain numerical threshold is reached for that assay). The user can choose to have all the sub- areas represented by the same color. The sub-areas and their assays can then still be distinguished by their relative location in the area.

By way of example, the invention typically is used to present the data from biochemical source arrays, such as 96-well (8 x 12) microtitre plates. The rectangular arrangement of the 8 x 12 array is an easy one to understand intuitively, and it also conveys important spatial information about the assay, so the graphical object typically mimics this rectangular arrangement, and thus is divided into areas that represent individual wells from the assay.

If only one assay, i.e., only one 96-well plate, is being presented by the graphical object, then a single gradation of gray or color within each area of the graphical object is used to represent the quantitative data from a well. For instance, if each test agent is being tested for solubility and blue is the color chosen, then light blue can be used to represent low solubility and dark blue can be used to represent high solubility (or vice- versa). The quantitative aspect of the data is preserved because different gradations of the color correspond to different quantitative results.

The multi-test assay itself has a two-dimensional characteristic (e.g., a two- dimensional arrangement of wells). If each test agent is screened with only the one assay, then we can think of this data as one-dimensional. One-dimensional data in a two-dimensional multi-test assay thus yields data three-dimensional data. A two- dimensional graphical object or table can convey the three-dimensional nature of the data, with the third dimension being encompassed by a gradation of color or gray (the current art providing only gradations of gray).

The present invention goes much further than the current art, in that it allows the user to present multi-dimensional data of four, five or more dimensions, yet the invention still relies on a simple two-dimensional graphical object that preserves readability by representing each quantitative assay by gradation of color or gray. The prior art does not The graphical object of the present invention also retains key information about the spatial arrangement of the test agents in the source arrays.

This preservation of spatial information is especially important because assays are rarely analyzed one at time. A scientist generally must analyze data from several related assays simultaneously in order to make informed experimental decisions. For instance, consider the case of a biochemist who is selecting candidate compounds for inhibition of two biochemical pathways, and at the same time selecting for high solubility. The biochemist generally carries out these three assays on three different plates, though they can be carried out on the same plate if they are physically compatible (which does not change the multi-dimensional nature of the data). It would clearly be extremely useful for the user to be able see all three of these results at once.

Thus the present invention provides for further sub-dividing each of the graphical object areas into sub-areas, each of which represents data for that particular agent as it is screened by a different assay for a different property. Thus, in the graphical object, data from the three plates can be combined, with the color red in one sub-area representing inhibition of pathway 1, green in another sub-area representing inhibition of pathway 2, and blue in a third sub-area representing solubility. The invention thus presents multidimensional data in a simple, two-dimensional graphical object that is easy to read. Just as important is the fact the rectangular arrangement preserves any spatial information inherent to the source assays.

Preserving the spatial information is important for two reasons, among others.

For one, the spatial arrangement often contains critical information about quality control.

For instance, if one particular pipette in the assay instrument is broken, it may result in faulty data for the particular well or set of wells serviced by that pipette. This problem will likely manifest itself as unusual data (often zero or negative data values) in those wells, and the user will often be able to recognize the problem because of the common spatial location of the unusual data across many source arrays. Second, important information about the experiment is often designed into the spatial arrangement of the assays. For instance, when screening a combinatorial chemical library for desired properties, the spatial relationship of the wells will generally be arranged to reflect structural activity relationships of the test agents. Each row of the source array might represent a different building block placed at one radical group position, while each column of the source array might represent a different building block placed at another radical group position. The fact that a particular building block might yield a consistent result in different molecules can thus easily be recognized by the user.

The user can display the actual numbers corresponding to the colored regions by moving the computer cursor over that area. The computer application also provides for a sort of "thermometer" to accompany the graphical object. The thermometer provides a visual reference for the colors displayed in the graphical object by displaying multiple standards with their numerical correlate (for instance, displaying the gradations of blue that correspond to 0 to 100% solubility in increments of 10%). The range of standards on the thermometer can be set by the user or chosen by the program based on the range of results. Note that the lightest gradation of color used will typically be the absence of that color. Thus the lightest gradation of blue, for instance, will typically be a default color, generally white, which counts as a "gradation" of blue for purposes of this invention.

A key aspect of the present invention is the flexibility of its display. While the concept of an easy-to-read, two-dimensional graphical object underlies the invention, within that concept the user can choose among a variety of embodiments of the graphical object in order to suit his experimental design and his personal preference in terms of display. For instance, it generally has been found that users prefer darker shades of color to mark the more interesting assay results, regardless of whether the result itself is quantitatively high or low, as darker colors seem to be easier to pick out of the rectangular array. Therefore, if a user is looking for a compound with high solubility but low inhibition- he will probably want to mark both high solubility and low inhibition with darker colors.

The user can also choose among a variety of colors and shapes for elements within the graphical object. Individual areas can be rectangles or circles, among other shapes. The areas themselves can be sub-divided into bars ("bar" mode) and sectors of a circle ("pie" mode), among shapes. Users can also design plug-in modules to incorporate additional display modes. The present invention allows the user to quickly switch between such display modes. Thus the invention is a flexible, data display application that enables the user to find the best mode of display for his experimental purposes.

FIG. 1 illustrates one example of a display window 100 and a graphical object

101 in accordance with the invention. In this particular example, the graphical object 101 is representing the results of three assays screened against test agents on 96-well assay plates (8 x 12). The well size 102 determines the size of the areas in the graphical object (normally in pixels) and is user-selected. The first assay 103 is listed along with user-selected minimum 104 and maximum 105 values, which define the upper and lower quantitative ranges to be displayed by the gradations of color. The all button 106 applies, for convenience, the minimum and maximum values for that assay to all the other assays. The options button 107 will be discussed below. Equivalents for elements 103-107 are provided for each assay being represented by the graphical object 101.

The data-plate number 108 is listed above the graphical object 101. A data-plate is to be distinguished from a source plate or source array, in that the latter is an actual physical plate, whereas a data plate can, and usually does, constitute the data from more than one plate, so as to be visually represented by the invention. The user selects the desired data plate from the data-plate selector 109. Each area 110 displays the data for the assays run on the particular test agent that corresponds to that area. A thermometer 111 is displayed below the graphical object 101. It presents the lightest and darkest color gradations to be used in the graphical object 101, along with a series of intermediate gradations for reference, for every color. Accompanying the thermometer are numerical correlates 112 for each of the gradations. Typically, the thermometer presents the numerical correlates of each assay in the same direction (e.g., low to high while moving left to right).

The user moves his cursor over a particular area to display detailed information about that area. This information includes the well number 113, the sample name 114, the well type 115, which is an additional piece of information about the area that can be uploaded with the data, and the score 116, which lists the numerical values for each of the assay results for that area.

hi the example illustrated in FIG. 1, the data-plate is being represented in "bulls- eye" mode. In this mode, the areas are circular, one assay is represented by a smaller circle in the center of the area, and the other assays are represented by concentric rings. In the example of FIG. 1, the assay Staph is represented by red and is the smaller centered circle, the assay E. coli is represented by green and is the inner concentric ring, and the assay Tox is represented by blue and is the outer concentric ring. FIG. 2 illustrates the same data-plate being displayed in "pie" mode, wherein each assay is represented by an unvarying sector of a circular area. FIG. 3 illustrates "bar" mode wherein each assay is represented by a horizontal bar in a rectangular area.

The pull-down menu "display mode" 900 of FIG. 9 and FIG. 4 is used to switch between display modes. These typically include the bull-eye mode 400, pie mode 401 and horizontal bar mode 402, which are listed in FIG. 4 and illustrated in FIGs. 1-3. Other display modes that are available to the user in this illustration of the present invention are vertical bar mode 403, stem mode-1 404 and stem mode-2 405, graph mode 406, bulls-eye+1 mode 407, pie+1 mode 408 and CV (coefficient of variation) mode 409. Vertical bar mode 403 is like horizontal bar mode 402, except with vertical bars, and is illustrated in FIG. 5. BuUs-eye+l mode and pie+1 mode are like JB mode and pie mode, respectively, except that one of the assays is assigned as a background sub-area in a square that surrounds the main circular part of the area. BuUs-eye+l mode and pie+1 mode are illustrated in FIGs. 6 and 7, respectively. These two modes are useful for viewing an assay that is unrelated to the main part of the overall assay (e.g., solubility, stability) as a "background" condition.

CV mode is a quick way of illustrating test agents that meet threshold conditions for one or more of the assays, hi CV mode, a zero threshold is automatically set using the average of all the test agents or a subset of them (e.g., the control wells) for a particular assay. All test agents that meet or exceed this zero for the assay are colored in one gradation and all the test agents that fall below this zero will be colored in another gradation. Alternatively, different colors can be used to distinguish between agents that fall above versus below the zero threshold.

Stem mode-1 404, stem mode-2 405 and graph mode 406 are slight variations on the main color representation system used in the present invention. Stem mode-1 represents quantitative differences by line segments differing in length, stem mode-2 represents quantitative differences by sections varying in area, and graph mode represents quantitative differences by varying y-coordinate heights. Numerous additional presentation modes are easily incorporated into the invention, h one embodiment, the invention is a Java-based computer application, and thus plug-in modules can easily be written by a developer or user and incorporated into the application.

When the user clicks one of options buttons 107 of FIG. 1, he is presented with an options window 800 in FIG. 8 for one of the assays. The options window 800 allows the user to specify whether the lower quantitative results 801 or the higher quantitative results 802 are represented by darker colors. The user can also choose to treat zero values as non-data 803 or as zero-value data 804. The user can choose to have non-data (null) wells specially marked 805, to have negative values specially marked 806 and to have bad quality-control wells specially marked 807. The data for whether a well has bad quality control is typically uploaded with the rest of data.

FIG. 9 shows some of the pull-down menus that are available, to the user, including display mode 900, edit criteria 901 and select 902. The user can use the edit criteria menu 901, to edit an existing criterion setting or to create a new one. In the example illustrated in FIG. 10, the user is setting the values for Criterion 1 in the set criteria window 1000. After these values are set, areas of the graphical object can then be specially marked based on whether they meet the values for this criterion. The criterion names 1001 are listed in a small window. The user selects one assay to set at a time, using an assay tab 1002. The user can then select the quantitative value range 1003 that must be met under Criterion 1 for that agent. The user can also set the value as a ratio 1004 to another agent in the assay.

After setting the values for all the assays in a criterion, the user can then select whether areas that meet this criterion should be specially marked or hidden, using element 1005. FIG 11 shows five areas, Gl, C2, G4, F6 A12 and B12 marked with a red frame as having met the selected criteria. FIG. 12 shows the same five areas as hidden. The user selects the criterion number to be applied with the select pull-down menu 902 of FIG. 9.

FIG. 13 illustrates how the visual representation system of the invention makes it an easy matter to sort through a large amount of complex multi-dimensional data. In the figure, an antagonist, or inhibition assay is being run on two 864-well plates, here represented in pie mode on an 864-area graphical object 1300. The red semi-circle on the right of each area represents inhibition of a specific biochemical pathway of interest to the researcher such as response to Tumor Necrosis Factor. The blue semi-circle on the left of each area represents inhibition of an unrelated pathway such as response to Human Growth Hormone. In both cases, darker colors have been chosen to mean higher inhibition. Areas E6 1301 and SI 1 1302 are dark on both sides. This means that the test agent being screened in these areas inhibit both pathways, and thus are probably non- specific inhibitors, e.g., poisons. Area M5 1303 shows inhibition only of response to Tumor Necrosis Factor, and thus may be a promising candidate for further research. The agent in area Ul 6 1304 is a specific inhibitor of response to Human Growth Hormone.

The areas in the bottom right corner of the graphical object that are dark on both sides are control wells. Finally, the group of areas near the top-right that all show similar results indicate a possible experimental problem such as an instrument malfunction, since they are coincidentally similar. For instance, the instrument might have failed to add the biochemical precursor necessary to the pathway, thus resulting in ' false inhibition readings. The data presentation format of the invention thus allows the user to quickly discern such possible problems and investigate them.

FIG. 14 shows how a combinatorial chemical library can be conveniently represented by the present invention. The two-dimensional graphical object shows part of that chemical library, based on a common chemical scaffold 1400, being assayed for three properties. The spatial arrangement of the source arrays is designed so that test agents with one particular chemical building block at the R_\ radical group position 1401 are placed in one column, while test agents with one particular chemical building block at the R₂ radical group position 1402 are placed in one row. When represented in the graphical object as shown, the user can easily see if a particular building block behaves consistently in different compounds, thus elucidating possible structural activity relationships, hi this figure, the graphical object is shown independent of the graphical display environment typical of the invention, and with the chemical building blocks 1402 and 1403 at R and R shown aligned with their respective graphical object areas, for illustrative purposes.

FIG. 15 is a flowchart representative of an exemplary graphical object 101 display. A process flow 1500 typically starts with a data or data file access 1501 and display of the graphical object window 1502. After the computer application receives the choice of data plate 1503 from the user, an example of the graphical object will be displayed 1504. At this point the user may select a different display mode 1505, enter a new well size 1506, or select a criteria setting 1507. The computer application will then redisplay the graphical object based on this new setting. The user may choose to change the color settings 1508, which opens a color setting window. After the user sets the colors 1509, the graphical object will be redrawn. The user may choose to edit the criteria or create new ones 1510. After the user enters these settings 1511, the graphical obj ect will be redrawn.

FIGs. 16A and 16B illustrate a computer system 1600 suitable for implementing embodiments of the present invention. FIG. 16A shows one possible physical form of the computer system. Of course, the computer system may have many physical forms ranging from an integrated circuit, a printed circuit board and a small handheld device up to a huge super computer. Computer system 1600 includes a monitor 1602, a display 1604, a housing 1606, a disk drive 1608, a keyboard 1610 and a mouse 1612. Disk 1614 is a computer-readable medium used to transfer data to and from computer system 1600.

FIG. 16B is an example of a block diagram for computer system 1600. Attached to system bus 1620 are a wide variety of subsystems. Processors) 1622 (also referred to as central processing units, or CPUs) are coupled to storage devices including memory 1624. Memory 1624 includes random access memory (RAM) and read-only memory (ROM). As is well known in the art, ROM acts to transfer data and instructions uni- directionally to the CPU and RAM is used typically to transfer data and instructions in a bi-directional manner. Both of these types of memories may include any suitable of the computer-readable media described below. N fixed disk 1626 is also coupled bi- directionally to CPU 1622; it provides additional data storage capacity and may also include any of the computer-readable media described below. Fixed disk 1626 may be used to store programs, data and the like and is typically a secondary storage medium (such as a hard disk) that is slower than primary storage. It will be appreciated that the information retained within fixed disk 1626, may, in appropriate cases, be incorporated in standard fashion as virtual memory in memory 1624. Removable disk 1614 may take the form of any of the computer-readable media described below.

CPU 1622 is also coupled to a variety of input/output devices such as display

1604, keyboard 1610, mouse 1612 and speakers 1630. hi general, an input/output device may be any of: video displays, track balls, mice, keyboards, microphones, touch- sensitive displays, transducer card readers, magnetic or paper tape readers, tablets, styluses, voice or handwriting recognizers, biometrics readers, or other computers. CPU 1622 optionally may be coupled to another computer or telecommunications network using network interface 1640. With such a network interface, it is contemplated that the CPU might receive information from the network, or might output information to the network in the course of performing the above-described method steps. Furthermore, method embodiments of the present invention may execute solely upon CPU 1622 or may execute over a network such as the Internet in conjunction with a remote CPU that shares a portion of the processing.

In addition, embodiments of the present invention further relate to computer storage products with a computer-readable medium that have computer code thereon for performing various computer-implemented operations such as inputting assay data, rendering that data in color graded representations in a graphical user interface, and acting on user inputs to affect display parameters of the data. The media and computer code may be those specially designed and constructed for the purposes of the present invention, or they may be of the kind well known and available to those having skill in the computer software arts. Examples of computer-readable media include, but are not limited to: magnetic media such as hard disks, floppy disks, and magnetic tape; optical media such as CD-ROMs and holographic devices; magneto-optical media such as floptical disks; and hardware devices that are specially configured to store and execute program code, such as application-specific integrated circuits (ASICs), programmable logic devices (PLDs), ROM and RAM devices, and signal transmission media for delivering computer-readable instructions, such as local area networks, wide area networks, and the Internet. Examples of computer code include machine code, such as produced by a compiler, and files containing higher level code that are executed by a computer using an interpreter. The invention also pertains to carrier waves and transport media on which the data and instructions of this invention may be transmitted.

Although the present invention has been discussed primarily in the context of visually representing microtitre, biochemical assay plates, the present invention is suitable for other data applications and may be tailored correspondingly. By way of example, the present invention may be adapted for analysis of other biochemical applications involving multi-test assays, such as the GeneChip™ by Affymetrix of Santa Clara, California, membrane-based arrays, and the like. The present invention can also be used for non-biochemical assays that involve multi-dimensional data. Although various details have been omitted for brevity's sake, obvious design alternatives may be implemented. Therefore, the present examples are to be considered as illustrative and not restrictive, and the invention is not to be limited to the details given herein, but may be modified within the scope of the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A computer system capable of visually displaying multi-dimensional quantitative data from a plurality of assays conducted on source arrays, the computer system comprising: one or more processors; one or more user input devices; a display capable of visually displaying the multi-dimensional data and associated information in particular ways responsive to input signals from one or more of the input devices and signals from one or more of the processors; and a graphical user interface running on one or more of the processors and providing a two-dimensional graphical object that represents the multi-dimensional data, wherein the two-dimensional graphical object comprises a plurality of areas, each area representing multiple assays of a particular test agent and comprising at least two sub- areas of color or gray, with each sub-area representing a particular assay conducted on the same test agent associated with the area, wherein gradations of the color or gray convey quantitative aspects of each assay.

2. The computer system of claim 1 wherein each sub-area is colored.

3. The computer system of claim 2 wherein each sub-area is colored with a different color.

4. The computer system of claim 1 wherein each area corresponds to a different test agent.

5. The computer system of claim 4 wherein each sub-area of each area corresponds to a different assay run on one of the test agents.

6. The computer system of claim 1 wherein the source arrays are testing media having discrete regions for separate biological, biochemical, or chemical tests.

7. The computer system of claim 1, wherein the source arrays are microtitre plates.

8. The computer system of claim 1 wherein the areas are rectangles.

9. The computer system of claim 1 wherein the areas are circles.

10. The computer system of claim 8 wherein the sub-areas are bars.

11. The computer system of claim 9 wherein the sub-areas include concentric rings.

12. The computer system of claim 9 wherein the sub-areas are pie sectors of a circle.

13. The computer system of claim 1 wherein at least one sub-area is graded more darkly to represent larger quantitative results.

14. The computer system of claim 1 wherein at least one sub-area is graded more darkly to represent smaller quantitative results.

15. The computer system of claim 1 wherein a gradation of color or gray represents a quantitative threshold with regard to one of the assays.

16. The computer system of claim 1 wherein an area that meets user-defined criteria regarding one or more of its assays is specially marked.

17. A computer system capable of visually displaying multi-dimensional quantitative assay data from source arrays, the computer system comprising: one or more processors; one or more user input devices; a display capable of visually displaying the multi-dimensional data and associated information in particular ways responsive to input signals from one or more of the input devices and signals from one or more of the processors; and a graphical user interface running on one or more of the processors and providing a two-dimensional graphical object that represents the multi-dimensional data as a plurality of areas displayed in an arrangement that conveys spatial information from the source arrays, wherein each source array comprises a plurality of test regions located at defined positions with respect to one another, and wherein each area in the graphical object represents a test region and the relative spatial location of each area in the graphical object corresponds to the relative spatial location of each test region within each source array.

18. The computer system of claim 17 wherein each area of the plurality of areas comprises at least two sub-areas of color or gray, wherein gradations of the color or gray convey quantitative aspects of the multi-dimensional data.

19. The computer system of claim 17 wherein the source arrays have a two- dimensional rectangular arrangement.

20. The computer system of claim 17 wherein the source arrays are testing media having discrete test regions for separate biological, biochemical, or chemical tests.

21. The computer system of claim 17 wherein the source arrays are microtitre plates.

22. A computer system capable of visually displaying multi-dimensional quantitative data from a plurality of assays conducted on source arrays, the computer system comprising: one or more processors; one or more user input devices; a display capable of visually displaying the multi-dimensional data and associated information in particular ways responsive to input signals from one or more of the input devices and signals from one or more of the processors; and a graphical user interface running on one or more of the processors and providing a two-dimensional graphical object that represents the multi-dimensional data, wherein the two-dimensional graphical object comprises a plurality of areas, each area representing multiple assays of a particular test agent and comprising at least two sub- areas, with each sub-area representing a particular assay conducted on the same test agent associated with the area, and wherein the sub-areas present visual information conveying quantitative aspects of each assay, and wherein the visual format of each area of the two-dimensional graphical object is selected by a user via input from a graphical user interface element or elements.

23. The computer system of claim 22 wherein each sub-area is color or gray, and wherein gradations of the color or gray convey quantitative aspects of each assay.

24. The computer system of claim 23 wherein each sub-area is colored with a different color.

25. The computer system of claim 22 wherein the source arrays have a two- dimensional rectangular arrangement.

26. The computer system of claim 22 wherein the source arrays are testing media having discrete regions for separate biological, biochemical, or chemical tests.

27. The computer system of claim 22 wherein the source arrays are microtitre plates.

28. The computer system of claim 27 wherein the list of visual formats further comprises at least one plug-in module visual format.

29. The computer system of claim 28 wherein at least one of the plug-in module visual formats is user-designed.

30. A method implemented on a computer system, the method visually representing multi-dimensional quantitative data from a plurality of assays conducted on source arrays, the method comprising: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data wherein the two-dimensional graphical object comprises a plurality of areas, each area representing multiple assays of a particular test agent and comprising at least two sub-areas of color or gray, with each sub-area representing a particular assay conducted on the same test agent associated with the area, wherein gradations of the color or gray are used to convey quantitative aspects of each assay.

31. The method of claim 30 wherein each sub-area is colored with a different color.

32. The method of claim 30 wherein each area corresponds to a different test agent.

33. The method of claim 30 wherein each sub-area corresponds to a different assay run on one of the test agents.

34. The method of claim 30 wherein the source arrays are testing media having discrete regions for separate biological, biochemical or chemical tests.

35. The method of claim 30 wherein the source arrays are microtitre plates.

36. A method implemented on a computer system, the method visually representing multi-dimensional quantitative data from a plurality of assays conducted on source arrays, each source array comprising a plurality of tests, the method comprising: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data as a plurality of areas displayed in an arrangement that conveys spatial information from the source arrays, wherein each source array comprises a plurality of test regions located at defined positions with respect to one another, and wherein each area in the graphical object represents a test region and the relative spatial locations of each area in the graphical object corresponds to the relative spatial locations of each test region within each source array.

37. The method of claim 36 wherein each area of the plurality of areas comprises at least two sub-areas of color or gray, wherein gradations of the color or gray are used to convey quantitative aspects of the multi-dimensional data.

38. The method of claim 37 wherein each sub-area is colored with a different color.

39. The method of claim 36 wherein the source arrays are testing media having discrete test regions for separate biological, biochemical or chemical tests.

40. A method implemented on a computer system, the method visually representing multi-dimensional quantitative data from a plurality of assays conducted on source arrays in multiple display modes, the method comprising: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data, wherein the two-dimensional graphical object comprises a plurality of areas, each area representing multiple assays of a particular test agent and comprising at least two sub-areas, with each sub-area representing a particular assay conducted on the same test agent associated with the area, and wherein the sub-areas present visual information conveying quantitative aspects of each assay, and wherein the visual format of each area of the two-dimensional graphical object is selected by a user via input from a graphical user interface element.

41. The method of claim 40 wherein each of the sub-areas is color or gray and wherein gradations of the color or gray are used to convey quantitative aspects of each assay.

42. The method of claim 41 wherein each sub-area is colored with a different color.

43. The method of claim 40 wherein the source arrays are testing media having discrete regions for separate biological, biochemical, or chemical tests.

44. The method of claim 40 wherein the source arrays are microtitre plates.

45. The method of claim 40 wherein the visual format of the two-dimensional graphical object is selected from a list comprising the following formats: graphical object with rectangular areas and bar sub-areas, graphical object with circular areas wherein each area has one smaller circular sub-area and at least one concentric ring sub- area, and graphical object with rectangular areas wherein at least one of the sub-areas is within a smaller circle contained within the rectangular area and one of the sub-areas is the background sub-area outside the smaller circle.

46. The method of claim 45 wherein the list of visual formats further comprises at least one plug-in module visual format.

47. The method of claim 46 wherein at least one of the plug-in module visual formats is user-designed.

48. A computer-program product comprising a computer-readable medium and program instructions provided via the computer-readable medium, the program instructions comprising instructions for visually representing multi-dimensional quantitative data, the instructions specifying: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data wherein the two-dimensional graphical object comprises a plurality of areas, each area representing multiple assays of a particular test agent and comprising at least two sub-areas of color or gray, with each sub-area representing a particular assay conducted on the same test agent associated with the area, wherein gradations of the color or gray are used to convey quantitative aspects of each assay.

49. The computer-program product of claim 48 wherein each sub-area is colored a different color.

50. The computer-program product of claim 48 wherein each area corresponds to a different test agent.

51. The computer-program product of claim 50 wherein each sub-area of each area corresponds to a different assay run on one of the test agents.

52. The computer-program product of claim 48 wherein the source arrays are testing media having discrete regions for separate biological, biochemical or chemical tests.

53. The computer-program product of claim 48 wherein the source arrays are microtitre plates.

54. A computer-program product comprising a computer-readable medium and program instructions provided via the computer-readable medium, the program instructions comprising instructions for visually representing multi-dimensional quantitative data, the instructions specifying: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data as a plurality of areas displayed in an arrangement that conveys spatial information from the source arrays, wherein each source array comprises a plurality of test regions located at defined positions with respect to one another, and wherein each area in the graphical object represents a test region and the relative spatial locations of each area in the graphical object corresponds to the relative spatial locations of each test region within each source array.

55. The computer-program product of claim 54 wherein each area of the plurality of areas comprises at least two sub-areas of color or gray, wherein gradations of the color or gray convey quantitative aspects of the multi-dimensional data.

56. The computer-program product of claim 55 wherein each sub-area is colored a different color.

57. The computer-program product of claim 54 wherein the source arrays are testing media having discrete test regions for separate biological, biochemical or chemical tests.

58. A computer-program product comprising a computer-readable medium and program instructions provided via the computer-readable medium, the program instructions comprising instructions for visually representing multi-dimensional quantitative data, the instructions specifying: receiving user input from a graphical user interface element to display the multidimensional data; and displaying a two-dimensional graphical object that represents the multidimensional data, wherein the two-dimensional graphical object comprises a plurality of areas, each representing multiple assays of a particular test agent and comprising at least two sub-areas, with each sub-area representing a particular assay conducted on the same test agent associated with the area, and wherein the sub-areas present visual information conveying quantitative aspects of each assay, and wherein the visual format of each area of the two-dimensional graphical object is selected by a user via input from a graphical user interface element.

59. The computer-program product of claim 58 wherein each sub-areas is color or gray and wherein gradations of the color or gray convey quantitative aspects of each assay.

60. The computer-program product of claim 59 wherein each sub-area is colored a different color.

61. The computer-program product of claim 58 wherein the source arrays are testing media having discrete regions for separate biological, biochemical, or chemical tests.

62. The computer-program product of claim 58 wherein the source arrays are microtitre plates.

63. The computer-program product of claim 58 wherein the visual format of the two-dimensional graphical object is selected from a list comprising the following formats: graphical object with rectangular areas and bar sub-areas, graphical object with circular areas wherein each area has one smaller circular sub-area and at least one concentric ring sub-area, and graphical object with rectangular areas wherein at least one of the sub-areas is within a smaller circle contained within the rectangular area and one of the sub-areas is the background sub-area outside the smaller circle.

64. The computer-program product of claim 63 wherein the list of visual formats further comprises at least one plug-in module visual format.

65. The computer-program product of claim 64 wherein at least one of the plug-in module visual formats is user-designed.

66. The computer system of claim 22 wherein the visual format of the two- dimensional graphical object is selected from a list including at least two of the following visual formats: graphical object with rectangular areas and bar sub-areas, graphical object with circular areas wherein each area has one smaller circular sub-area and at least one concentric ring sub-area, and graphical object with rectangular areas wherein at least one of the sub-areas is within a smaller circle contained within the rectangular area and one of the sub-areas is the background sub-area outside the smaller circle.