US2013169645A1PendingUtilityA1

Computer-aided visualization of expression comparison

Assignee: AFFYMETRIX INCPriority: Dec 11, 1997Filed: Sep 25, 2012Published: Jul 4, 2013
Est. expiryDec 11, 2017(expired)· nominal 20-yr term from priority
G06T 11/26C12N 15/1089G16B 45/00G16B 25/00C12Q 1/68G16B 25/10G06T 11/206
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Claims

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

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A computer implemented method of presenting expression level information as collected from first and second samples, said method comprising the steps of:
 displaying a first axis corresponding to expression level in said first sample;   displaying a second axis substantially perpendicular to said first axis, said second axis corresponding to expression level in said second sample; and   for a selected expressed sequence, displaying a mark at a position, 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.   
     
     
         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 the step of repeating said displaying a mark step for a plurality of selected expressed sequences. 
     
     
         5 . The method of  claim 1  further comprising the steps of:
 monitoring said expression level of said expressed sequence in said first sample and said second sample. 
 
     
     
         6 . The method of  claim 3  wherein said monitoring step for one of said samples comprises substeps of:
 inputting a plurality of hybridization intensities of 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 step. 
 
     
     
         7 . The method of  claim 6  further comprising the step of:
 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 the step of:
 comparing a quotient of hybridization intensities of perfect match and 3 mismatch probes at a base position to a ratio threshold. 
 
     
     
         9 . The method of  claim 6  further comprising the steps of:
 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; and 
 c) computing a logarithmic ratio of said perfect match probe intensity to said mismatch probe intensity. 
 
     
     
         10 . The method of  claim 9  further comprising the steps of:
 repeating said a), b), and c) steps for each of said probe pairs, accumulating a sum of differences of said perfect match and mismatch probe intensities for probe pairs that cause; and 
 determining an expression level of said selected expressed sequence to be an average of said differences. 
 
     
     
         11 . The method of  claim 1  further comprising the steps of:
 receiving user input selecting said mark; and 
 in response to said user input, displaying information about said selected expressed sequence. 
 
     
     
         12 . The method of  claim 11  further comprising the steps of:
 in response to said user input, displaying information about said selected expressed sequence. 
 
     
     
         13 . The method of  claim 12  wherein said information about said selected expressed sequence comprises a GenBank accession number. 
     
     
         14 . The method of  claim 12  wherein said information about said selected expressed sequence comprises a GenBank database record for said selected expressed sequence. 
     
     
         15 . The method of  claim 1  wherein said first sample and said second sample are collected from tissue samples differing in a particular characteristic. 
     
     
         16 . The method of  claim 15  wherein said particular characteristic comprises presence of disease. 
     
     
         17 . The method of  claim 15  wherein said particular characteristic comprises a treatment strategy for a disease. 
     
     
         18 . The method of  claim 1  wherein said particular characteristic is a stage of a disease. 
     
     
         19 . The method of  claim 1  further comprising the step of:
 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. 
 
     
     
         20 . A computer implemented method of presenting sample analysis information comprising the steps of:
 displaying a first axis corresponding to 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 corresponding to 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, 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.   
     
     
         21 . The method of  claim 20  wherein said selected polymer comprises a nucleic acid sequence. 
     
     
         22 . The method of  claim 20  wherein said selected polymer comprises a protein. 
     
     
         23 . The method of  claim 21  further comprising the step of:
 obtaining said concentration of said compound in said first sample by exposing said first sample to a plurality of nucleic acid probes. 
 
     
     
         24 . The method of  claim 22  further comprising the step of:
 obtaining said concentration of said compound in said first sample by exposing said first sample to a plurality of peptide probes. 
 
     
     
         25 . A computer program product for presenting expression level information as collected from first and second samples, said product comprising:
 code for displaying a first axis corresponding to expression level in said first sample;   code for displaying a second axis substantially perpendicular to said first axis, said second axis corresponding to expression level in said second sample;   code for, for a selected expressed sequence, displaying a mark at a position, 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; and a computer readable storage medium for storing the codes.   
     
     
         26 . The product of  claim 25  wherein said selected expressed sequence comprises a gene. 
     
     
         27 . The product of  claim 25  wherein said selected expressed sequence comprises a portion of a gene. 
     
     
         28 . The product of  claim 25  further comprising code for repeatedly applying said displaying a mark code for a plurality of selected expressed sequences. 
     
     
         29 . The product of  claim 25  further comprising: code for monitoring said expression level of said expressed sequence in said first sample and said second sample. 
     
     
         30 . The product of  claim 27  wherein said monitoring step for one of said samples comprises:
 code for inputting a plurality of hybridization intensities of 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 step. 
 
     
     
         31 . The product of  claim 30  further comprising:
 code for comparing a difference between hybridization intensities of perfect match and mismatch probes at a base position to a difference threshold. 
 
     
     
         32 . The product of  claim 31  further comprising:
 code for comparing a quotient of hybridization intensities of perfect match and mismatch probes at a base position to a ratio threshold. 
 
     
     
         33 . The product of  claim 30  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 intensity to said mismatch probe intensity. 
 
     
     
         34 . The product of  claim 33  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 cause; and 
 code for determining an expression level of said selected expressed sequence to be an average of said differences. 
 
     
     
         35 . The product of  claim 25  further comprising:
 code for receiving user input selecting said mark; and 
 code for, in response to said user input, displaying information about said selected expressed sequence. 
 
     
     
         36 . The product of  claim 35  further comprising:
 code for, in response to said user input, displaying information about said selected expressed sequence. 
 
     
     
         37 . The product of  claim 36  wherein said information about said selected expressed sequence comprises a GenBank accession number. 
     
     
         38 . The product of  claim 36  wherein said information about said selected expressed sequence comprises a GenBank database record for said selected expressed sequence. 
     
     
         39 . The product of  claim 25  wherein said first sample and said second sample are collected from tissue samples differing in a particular characteristic. 
     
     
         40 . The product of  claim 39  wherein said particular characteristic comprises presence of disease. 
     
     
         41 . The product of  claim 39  wherein said particular characteristic comprises a treatment strategy for a disease. 
     
     
         42 . The product of  claim 25  wherein said particular characteristic is a stage of a disease. 
     
     
         43 . The product of  claim 25  further comprising the step of:
 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. 
 
     
     
         44 . A computer program product for presenting sample analysis information comprising:
 code for displaying a first axis corresponding to 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 corresponding to 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, 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; and   a computer readable storage medium that stores the codes.   
     
     
         45 . The product of  claim 44  wherein said selected polymer comprises a nucleic acid sequence. 
     
     
         46 . The product of  claim 44  wherein said selected polymer comprises a protein. 
     
     
         47 . A computer system comprising a display, a processor, and a memory that stores instructions for configuring said processor to:
 display a first axis corresponding to expression level in said first sample;   display a second axis substantially perpendicular to said first axis, said second axis corresponding to expression level in said second sample; and   for a selected expressed sequence, display a mark at a position, 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.   
     
     
         48 . A computer system comprising a display, a processor, and a memory that stores instructions for configuring said processor to:
 display a first axis corresponding to 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 corresponding to 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, 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.

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