US2006154273A1PendingUtilityA1

System and Computer Software Products for Comparative Gene Expression Analysis

58
Assignee: AFFYMETRIX INCPriority: Dec 12, 2000Filed: Mar 22, 2006Published: Jul 13, 2006
Est. expiryDec 12, 2020(expired)· nominal 20-yr term from priority
G16B 25/10G16B 25/00
58
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Methods and computer software products are provided for analyzing gene expression data. In one embodiment, methods, systems and computer software are provided for comparative gene expression analysis using intensity dependent normalization factors.

Claims

exact text as granted — not AI-modified
1 - 6 . (canceled)  
   
   
       7 . A computer implemented method for comparing the expression of a gene in a first sample with a second sample comprising: 
 providing a first plurality of intensity values (I i   (1) ), each of which reflects the expression of said gene in said first sample, wherein said intensity values are obtained from a first nucleic acid probe array;    providing a second plurality of intensity values (I i   2) ), each of which reflects the expression of said gene in said second sample, wherein said intensity values are obtained from a second nucleic acid probe array;    calculating a p-value using one-sided Wilcoxon's signed rank test, wherein the p-value is for anull hypothesis that medianf(x)I i   (2) −I i   (1) )=0 and an alternative hypothesis that median((f((x)I i   (1) −I i   (2) )>0, wherein saidf(x) is a normalization factor; and    indicating whether said transcript is present based upon said p-value.    
   
   
       8 . The method of  claim 7  further comprising a step of calculating normalization factor, said step comprising: 
 obtaining the geometric mean (x) of said I i   (1)  and said I i   (2) ;    calculating said normalization factor according to:    f(x)=e h(x) , wherein said h(x) is derived from referential intensities from said first and second probe arrays.    
   
   
       9 . The method of  claim 8  wherein said h(x) is derived by relating geometric means (x i ′) of first referential intensities (RI i   (1) ) in said first probe array and said second referential intensities (RI i   (2) ) in said second probe array to:  
     
       
         
           
             
               y 
               i 
               ′ 
             
             = 
             
               log 
               ⁢ 
               
                   
               
               ⁢ 
               
                 
                   ( 
                   
                     
                       RI 
                       i 
                       
                         ( 
                         1 
                         ) 
                       
                     
                     
                       RI 
                       i 
                       
                         ( 
                         2 
                         ) 
                       
                     
                   
                   ) 
                 
                 . 
               
             
           
         
       
     
   
   
       10 . The method of  claim 9  wherein said relating comprising: 
 sorting (x i , y i ) pairs according to x i  into a plurality (m number) of bins with no overlapping;    computing medians ({overscore (x)} k ) of x i 's and medians ({overscore (y)} k ) of y i 's for each bin; and    interpolating said medians ({overscore (x)} k , {overscore (y)} k ).    
   
   
       11 . The method of  claim 10  wherein said bins are of approximately equal size.  
   
   
       12 . The method of  claim 11  wherein said h(x) is:  
     
       
         
           
             
               h 
               ⁡ 
               
                 ( 
                 x 
                 ) 
               
             
             = 
             
               { 
               
                 
                   
                     
                       
                         
                           y 
                           _ 
                         
                         1 
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         ≤ 
                         
                           
                             x 
                             _ 
                           
                           1 
                         
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             w 
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               1 
                             
                           
                           + 
                           
                             
                               ( 
                               
                                 1 
                                 - 
                                 w 
                               
                               ) 
                             
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               
                                 i 
                                 + 
                                 1 
                               
                             
                           
                         
                         , 
                       
                     
                   
                   
                     
                       
                           
                         ⁢ 
                         
                           
                             if 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             x 
                           
                           ∈ 
                           
                             ( 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 i 
                               
                               , 
                               
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                                 + 
                                 1 
                               
                             
                           
                         
                         ] 
                       
                       , 
                     
                   
                 
                 
                   
                     
                       
                         w 
                         = 
                         
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               - 
                               x 
                             
                           
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               + 
                               
                                 - 
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                               
                             
                           
                         
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           i 
                           = 
                           1 
                         
                         , 
                         … 
                         ⁢ 
                         
                             
                         
                         , 
                         
                           m 
                           - 
                           1 
                         
                         , 
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             y 
                             _ 
                           
                           m 
                         
                         , 
                       
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         > 
                         
                           
                             
                               x 
                               _ 
                             
                             m 
                           
                           . 
                         
                       
                     
                   
                 
               
             
           
         
       
     
   
   
       13 . The method of  claim 12  wherein said m is 3.  
   
   
       14 - 19 . (canceled)  
   
   
       20 . A system for comparing the expression of a gene in a first sample with a second sample comprising: 
 a processor; and    a memory coupled with the processor, the memory storing a plurality of machine instructions that cause the processor to perform a plurality of logical steps when implemented by the processor, the logical steps comprising:    providing a first plurality of intensity values (I i   (1) ), each of which reflects the expression of said gene in said first sample, wherein said intensity values are obtained from a first nucleic acid probe array;    providing a second plurality of intensity values (I i   (2) ), each of which reflects the expression of said gene in said second sample, wherein said intensity values are obtained from a second nucleic acid probe array;    calculating ap-value using one-sided Wilcoxon's signed rank test, wherein the p-value is for a null hypothesis that median(f(x)I i   (2) −I i   (1) )=0 and an alternative hypothesis that median((f(x)I i   (1) −I i   (2) )>0, wherein said f(x) is a normalization factor; and    indicating whether said transcript is present based upon said p-value.    
   
   
       21 . The system of  claim 20  further comprising a step of calculating normalization factor, said step comprising: 
 obtaining the geometric mean (x) of said I i   (1)  and said I i   (2)     ;    calculating said normalization factor according to:    f(x)=e h(x) , wherein said h(x) is derived from referential intensities from said first and second probe arrays.    
   
   
       22 . The system of  claim 21  wherein said h(x) is derived by relating geometric means (x i ′) of first referential intensities (RI i   (1) ) in said first probe array and said second referential intensities (RI i   (2) ) in said second probe array to:  
     
       
         
           
             
               y 
               i 
               ′ 
             
             = 
             
               log 
               ⁢ 
               
                   
               
               ⁢ 
               
                 
                   ( 
                   
                     
                       RI 
                       i 
                       
                         ( 
                         1 
                         ) 
                       
                     
                     
                       RI 
                       i 
                       
                         ( 
                         2 
                         ) 
                       
                     
                   
                   ) 
                 
                 . 
               
             
           
         
       
     
   
   
       23 . The system of  claim 22  wherein said relating comprising: 
 sorting (x i , y i ) pairs according to x i  into a plurality (m number) of bins with no overlapping;    computing medians ({overscore (x)} k ) of x i 's and medians ({overscore (y)} k ) of y i 's for each bin; and    interpolating said medians ({overscore (x)} k , {overscore (y)} k ).    
   
   
       24 . The system of  claim 23  wherein said bins are of approximately equal size.  
   
   
       25 . The system of  claim 24  wherein said h(x) is:  
     
       
         
           
             
               h 
               ⁡ 
               
                 ( 
                 x 
                 ) 
               
             
             = 
             
               { 
               
                 
                   
                     
                       
                         
                           y 
                           _ 
                         
                         1 
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         ≤ 
                         
                           
                             x 
                             _ 
                           
                           1 
                         
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             w 
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               1 
                             
                           
                           + 
                           
                             
                               ( 
                               
                                 1 
                                 - 
                                 w 
                               
                               ) 
                             
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               
                                 i 
                                 + 
                                 1 
                               
                             
                           
                         
                         , 
                       
                     
                   
                   
                     
                       
                           
                         ⁢ 
                         
                           
                             if 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             x 
                           
                           ∈ 
                           
                             ( 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 i 
                               
                               , 
                               
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                                 + 
                                 1 
                               
                             
                           
                         
                         ] 
                       
                       , 
                     
                   
                 
                 
                   
                     
                       
                         w 
                         = 
                         
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               - 
                               x 
                             
                           
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               + 
                               
                                 - 
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                               
                             
                           
                         
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           i 
                           = 
                           1 
                         
                         , 
                         … 
                         ⁢ 
                         
                             
                         
                         , 
                         
                           m 
                           - 
                           1 
                         
                         , 
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             y 
                             _ 
                           
                           m 
                         
                         , 
                       
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         > 
                         
                           
                             
                               x 
                               _ 
                             
                             m 
                           
                           . 
                         
                       
                     
                   
                 
               
             
           
         
       
     
   
   
       26 . The system of  claim 25  wherein said m is 3.  
   
   
       27 - 32 . (canceled)  
   
   
       33 . A computer software product for comparing the expression of a gene in a first sample with a second sample comprising: 
 computer program code for providing a first plurality of intensity values (I i   (1) ), each of which reflects the expression of said gene in said first sample, wherein said intensity values are obtained from a first nucleic acid probe array;    computer program code for providing a second plurality of intensity values (I i   (2) ), each of which reflects the expression of said gene in said second sample, wherein said intensity values are obtained from a second nucleic acid probe array;    computer program code for calculating a p-value using one-sided Wilcoxon's signed rank test, wherein the p-value is for a null hypothesis that median(f(x)I i   (2) −I i   (1) )=0 and an alternative hypothesis that median((f(x)I i   (1) −I i   (2) )>0, wherein said f(x) is a normalization factor;    computer program code for indicating whether said transcript is present based upon said p-value; and    a computer readable medium for storing said codes.    
   
   
       34 . The computer program code of  claim 33  further comprising computer program code for calculating normalization factor, said code comprising: 
 code for obtaining the geometric mean (x) of said I i   (1)  and said I i   (2) ;    code for calculating said normalization factor according to:    f(x)=e h(x) , wherein said h(x) is derived from referential intensities from said first and second probe arrays.    
   
   
       35 . The computer software product of  claim 34  wherein said h(x) is derived by relating geometric means (x i ′) of first referential intensities (RI i   (1) ) in said first probe array and said second referential intensities (RI i   (2) ) in said second probe array to:  
     
       
         
           
             
               y 
               i 
               ′ 
             
             = 
             
               log 
               ⁢ 
               
                   
               
               ⁢ 
               
                 
                   ( 
                   
                     
                       RI 
                       i 
                       
                         ( 
                         1 
                         ) 
                       
                     
                     
                       RI 
                       i 
                       
                         ( 
                         2 
                         ) 
                       
                     
                   
                   ) 
                 
                 . 
               
             
           
         
       
     
   
   
       36 . The computer software product of  claim 35  wherein said code for relating comprising: 
 computer code for sorting (x i , y i ) pairs according to xi into a plurality (m number) of bins with no overlapping;    computer code for computing medians ({overscore (x)} k ) of x i 's and medians ({overscore (y)} k ) of y i 's for each bin; and    computer code for interpolating said medians ({overscore (x)} k , {overscore (y)} k ).    
   
   
       37 . The computer software product of  claim 36  wherein said bins are of approximately equal size.  
   
   
       38 . The computer software product of  claim 37  wherein said h(x) is:  
     
       
         
           
             
               h 
               ⁡ 
               
                 ( 
                 x 
                 ) 
               
             
             = 
             
               { 
               
                 
                   
                     
                       
                         
                           y 
                           _ 
                         
                         1 
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         ≤ 
                         
                           
                             x 
                             _ 
                           
                           1 
                         
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             w 
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               1 
                             
                           
                           + 
                           
                             
                               ( 
                               
                                 1 
                                 - 
                                 w 
                               
                               ) 
                             
                             ⁢ 
                             
                               
                                 y 
                                 _ 
                               
                               
                                 i 
                                 + 
                                 1 
                               
                             
                           
                         
                         , 
                       
                     
                   
                   
                     
                       
                           
                         ⁢ 
                         
                           
                             if 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             x 
                           
                           ∈ 
                           
                             ( 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 i 
                               
                               , 
                               
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                                 + 
                                 1 
                               
                             
                           
                         
                         ] 
                       
                       , 
                     
                   
                 
                 
                   
                     
                       
                         w 
                         = 
                         
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               - 
                               x 
                             
                           
                           
                             
                                 
                             
                             ⁢ 
                             
                               
                                 
                                   x 
                                   _ 
                                 
                                 
                                   i 
                                   + 
                                   1 
                                 
                               
                               + 
                               
                                 - 
                                 
                                   
                                     x 
                                     _ 
                                   
                                   i 
                                 
                               
                             
                           
                         
                       
                       , 
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           i 
                           = 
                           1 
                         
                         , 
                         … 
                         ⁢ 
                         
                             
                         
                         , 
                         
                           m 
                           - 
                           1 
                         
                         , 
                       
                     
                   
                 
                 
                   
                     
                         
                       ⁢ 
                       
                         
                           
                             y 
                             _ 
                           
                           m 
                         
                         , 
                       
                     
                   
                   
                     
                         
                       ⁢ 
                       
                         
                           if 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           x 
                         
                         > 
                         
                           
                             
                               x 
                               _ 
                             
                             m 
                           
                           . 
                         
                       
                     
                   
                 
               
             
           
         
       
     
   
   
       39 . The computer software product of  claim 38  wherein said m is 3.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.