Computer-aided display for comparative gene expression

• US 6,420,108 B2
• Filed: 02/09/1998
• Issued: 07/16/2002
• Est. Priority Date: 02/09/1998
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Snyder, Jim, Gish, Kurt, Mack, David H., Dai, Josie, Balaban, David, Khurgin, Elina
• Primary Examiner(s): Siew, Jeffrey
• Application Number:
  US09/020,743
• Publication Number:
  US 20020015948A1
• Time in Patent Office: 1,618 Days
• Field of Search: 435/6, 435/7.1, 536/24.3, 536/24.31, 536/24.33, 702/19, 702/20
• US Class Current: 435/6.1
• CPC Class Codes: C12N 15/1089 Design, preparation, screening or analysis of libraries using computer algorithms
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: G06T 11/206 Drawing of charts or graphs
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 45/00 ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks

Abstract

Innovative systems and methods for visualizing information collected from analyzing samples are provided. The samples may include nucleic acids, proteins, or other polymers. Gene expression level as determined from analysis of a nucleic acid sample is one possible analysis result that may be visualized. In one embodiment, a computer system may display the expression levels of multiple genes simultaneously in a way that facilitates user identification of genes whose expression is significant to a characteristic such as disease or resistance to disease. Additionally, the computer system may facilitate display of further information about relevant genes once they are identified.

Claims

1. A computer-implemented method of presenting expression level information as collected from first and second samples, said method comprising:

displaying a first axis indicating expression level in said first sample;

displaying a second axis substantially perpendicular to said first axis, said second axis indicating expression level in said second sample;

for a selected expressed sequence, displaying a mark at a position with an X coordinate and a Y coordinate, wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with an expression level of said selected expressed sequence in said first sample and relative to said second axis in accordance with an expression level of said selected expressed sequence in said second sample;

receiving an input of a user'"'"'s selection of said mark; and

in response to said user input, displaying information about said selected expressed sequence.

2. The method of claim 1 wherein said selected expressed sequence comprises a gene.

3. The method of claim 1 wherein said selected expressed sequence comprises a portion of a gene.

4. The method of claim 1 further comprising;

repeatedly displaying a mark for each one of a plurality of selected expressed sequences.

5. The method of claim 1 further comprising:

monitoring said expression level of said expressed sequence in said first sample and said second sample.

14. The method of claim 1 wherein said first sample and said second sample are collected from tissue samples differing in a particular characteristic.

15. The method of claim 14 wherein said particular characteristic comprises a disease state.

16. The method of claim 14 wherein said particular characteristic comprises a treatment strategy for a disease.

17. The method of claim 1 wherein said particular characteristic is a stage of a disease.

18. The method of claim 1 further comprising:

displaying a third axis substantially perpendicular to said first axis and to said second axis in a three-dimensional display environment wherein said position of said mark is further selected relative to said third axis in accordance with an expression level of said selected expressed sequence in a third sample.

47. The method of claim 1 further comprising:

providing a tactile feedback to said user through a pointing device when a cursor is moved over said mark;

said tactile feedback indicating expression level for said selected expressed sequence corresponding to said mark.

48. The method of claim 1 further comprising:

providing an aural indication to said user through a pointing device when a cursor is moved over said mark;

said aural indication indicating expression level for said selected expressed sequence corresponding to said mark.

49. The method of claim 1 further comprising:

obtaining information from an internet based resource about a selected expressed sequence corresponding to said mark.

50. The method of claim 1 further comprising:

receiving from the user a selection of at least two of a plurality of marks, said marks;

displaying information about genes corresponding to said selection of at least two of a plurality of marks.

6. The method of claim wherein said monitoring further comprises

inputting a plurality of hybridization intensities from pairs of perfect match and mismatch probes, said perfect match probes being perfectly complementary to a target nucleic acid sequence indicative of expression of said selected gene and said mismatch probes having at least one base mismatch with said target sequence, and said hybridization intensities indicating hybridization affinity between said perfect match and mismatch probes and a sample nucleic acid sequence from said one of said samples;

comparing the hybridization intensities of each pair of perfect match probe and mismatch probe; and

generating said expression level for said expressed sequence and said one of said samples responsive to results of said comparing.

7. The method of claim 6 further comprising

comparing a difference between hybridization intensities of perfect match and mismatch probes at a base position to a difference threshold.

8. The method of claim 7 further comprising:

comparing a quotient of hybridization intensities of perfect match and mismatch probes at a base position to a ratio threshold.

9. The method of claim 6 further comprising:

a) counting a probe pair as a positive probe pair to increment a positive probe pair count if a perfect match probe intensity minus a mismatch probe intensity exceeds a difference threshold and said perfect match probe intensity divided by said mismatch probe intensity exceeds a ratio threshold;

b) counting said probe pair as a negative probe pair to increment a negative probe pair count if said mismatch probe intensity minus said perfect match probe intensity exceeds said difference threshold and said mismatch probe intensity divided by said perfect match probe intensity exceeds said ratio threshold;

c) computing a logarithmic ratio of said perfect match probe intensity to said mismatch probe intensity; and

d) computing a difference of said perfect match probe intensity to said mismatch probe intensity.

10. The method of claim 9 further comprising:

repeating said a), b), c) and d) steps for each of said probe pairs, accumulating a sum of differences of said perfect match and mismatch probe intensities for probe pairs that exhibit said difference; and

determining an expression level of said selected expressed sequence to be an average of said differences.

11. The method of claim 11 further comprising:

in response to said input, displaying information about said selected expressed sequence;

said information comprising an identifier for said selected expressed sequence.

12. The method of claim 11 wherein said identifier for said selected expressed sequence comprises a GenBank accession number.

13. The method of claim 11 wherein said information about said selected expressed sequence comprises a GenBank database record for said selected expressed sequence.

19. A computer-implemented method of presenting sample analysis information comprising:

displaying a first axis indicating a concentration of a compound in a first sample as determined by monitoring binding of said compound to a selected polymer having binding affinity to said compound;

displaying a second axis substantially perpendicular to said first axis, said second axis indicating a concentration of said compound in said second sample as determined by monitoring binding of said compound to said selected polymer; and

displaying a mark at a position with an X coordinate and a Y coordinate, wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with said concentration in said first sample and relative to said second axis in accordance with said concentration in said second samples;

receiving an input of a user'"'"'s selection of said mark; and

in response to said user input displaying information about said compound.

20. The method of claim 19 wherein said selected polymer comprises a nucleic acid sequence.

21. The method of claim 19 wherein said selected polymer comprises a protein.

22. The method of claim 20 further comprising:

obtaining said concentration of said compound in said first sample by exposing said first sample to a plurality of nucleic acid probes.

23. The method of claim 21 further comprising:

obtaining said concentration of said compound in said first sample by exposing said first sample to a plurality of peptide probes.

24. A computer program product for presenting expression level information as collected from a first sample and a second sample, said product comprising:

code for displaying a first axis indicating expression level in said first sample;

code for displaying a second axis substantially perpendicular to said first axis, said second axis indicating expression level in said second sample;

code for, for a selected expressed sequence, displaying a mark at a position with an X coordinate and a Y coordinate wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with an expression level of said selected expressed sequence in said first sample and relative to said second axis in accordance with an expression level of said selected expressed sequence in said second sample;

code for receiving an input from a user'"'"'s selection of said mark;

code for displaying information about said selected expressed sequence in response to said user input; and

a computer-readable storage medium for storing the codes.

25. The product of claim 24 wherein said selected expressed sequence comprises a gene.

26. The product of claim 24 wherein said selected expressed sequence comprises a portion of a gene.

27. The product of claim 24 further comprising code for repeatedly applying said displaying a mark code for a plurality of selected expressed sequences.

28. The product of claim 24 further comprising:

code for monitoring said expression level of said expressed sequence in said first sample and said second sample.

29. The product of claim 28 wherein said code for monitoring for one of said samples comprises:

code for inputting a plurality of hybridization intensities from pairs of perfect match and mismatch probes, said perfect match probes being perfectly complementary to a target nucleic acid sequence indicative of expression of said selected gene and said mismatch probes having at least one base mismatch with said target sequence, and said hybridization intensities indicating hybridization affinity between said perfect match and mismatch probes and a sample nucleic acid sequence from said one of said samples;

code for comparing the hybridization intensities of each pair of perfect match probe and mismatch probe; and

code for generating said expression level for said expressed sequence and said one of said samples responsive to a result produced by said code for comparing.

30. The product of claim 29 further comprising:

code for comparing a difference between hybridization intensities of perfect match and mismatch probes at a base position to a difference threshold.

31. The product of claim 30 further comprising:

code for comparing a quotient of hybridization intensities of perfect match and mismatch probes at a base position to a ratio threshold.

32. The product of claim 29 further comprising:

a) code for counting a probe pair as a positive probe pair to increment a positive probe pair count if a perfect match probe intensity minus a mismatch probe intensity exceeds a difference threshold and said perfect match probe intensity divided by said mismatch probe intensity exceeds a ratio threshold;

b) code for counting said probe pair as a negative probe pair to increment a negative probe pair count if said mismatch probe intensity minus said perfect match probe intensity exceeds said difference threshold and said mismatch probe intensity divided by said perfect match probe intensity exceeds said ratio threshold; and

c) code for computing a logarithmic ratio of said perfect match probe to intensity to said mismatch probe intensity.

33. The product of claim 32 further comprising:

code for repeatedly applying said a), b), and c) codes for each of said probe pairs, accumulating a sum of differences of said perfect match and mismatch probe intensities for probe pairs that exhibit said difference; and

code for determining an expression level of said selected expressed sequence to be an average of said differences.

34. The product of claim 24 further comprising:

code for, in response to said input, displaying information about said selected expressed sequence;

said information comprising an identifier for said selected expressed sequence.

35. The product of claim 34 wherein said identifier for said selected expressed sequence comprises a GenBank accession number.

36. The product of claim 34 wherein said information about said selected expressed sequence comprises a GenBank database record for said selected expressed sequence.

37. The product of claim 24 wherein said first sample and said second sample are collected from tissue samples differing in a particular characteristic.

38. The product of claim 37 wherein said particular characteristic comprises a disease state.

39. The product of claim 37 wherein said particular characteristic comprises a treatment strategy for a disease.

40. The product of claim 37 wherein said particular characteristic is a stage of a disease.

41. The product of claim 24 further comprising:

code for displaying a third axis substantially perpendicular to said first axis and to said second axis in a three-dimensional display environment wherein said position of said mark is further selected relative to said third axis in accordance with an expression level of said selected expressed sequence in a third sample.

42. A computer program product for presenting sample analysis information comprising:

code for displaying a first axis indicating a concentration of a compound in a first sample as determined by monitoring binding of said compound to a selected polymer having bonding affinity to said compound;

code for displaying a second axis substantially perpendicular to said first axis, said second axis indicating a concentration of said compound in a second sample as determined by monitoring binding of said compound to said selected polymer;

code for displaying a mark at a position with an X coordinate and a Y coordinate wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with said concentration in said first sample and relative to said second axis in accordance with said concentration in said second sample;

code for receiving an input of a user'"'"'s selection of said mark;

code for displaying information about said compound in response to said user input; and

a computer-readable storage medium that stores the codes.

43. The product of claim 42 wherein said selected polymer comprises a nucleic acid sequence.

44. The product of claim 42 wherein said selected polymer comprises a protein.

45. A computer system comprising a display, a processor, and a memory that stores instructions for configuring said processor to:

display a first axis indicating expression level in said first sample;

display a second axis substantially perpendicular to said first axis, said second axis indicating expression level in said second sample; and

for a selected expressed sequence, display a mark at a position with an X coordinate and a Y coordinate, wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with an expression level of said selected expressed sequence in said first sample and relative to said second axis in accordance with an expression level of said selected expressed sequence in said second sample;

wherein information about said selected expressed sequence is displayed responsive to an input of a user'"'"'s selection of said mark.

46. A computer system comprising a display, a processor, and a memory that stores instructions for configuring said processor to:

display a first axis indicating a concentration of a compound in a first sample as determined by monitoring binding of said compound to a selected polymer having binding affinity to said compound;

display a second axis substantially perpendicular to said first axis, said second axis indicating a concentration of said compound in said second sample as determined by monitoring binding of said compound to said selected polymer; and

display a mark at a position with an X coordinate and a Y coordinate, wherein the X coordinate of said position is selected relative to said first axis and said Y coordinate of said position is selected relative to said second axis, wherein said position is selected relative to said first axis in accordance with said concentration in said first sample and relative to said second axis in accordance with said concentration in said second sample;

wherein information about said selected expressed sequence is displayed responsive to an input of a user'"'"'s selection of said mark.