US2012323497A1PendingUtilityA1
Non-Hypergeometric Overlap Probability
Est. expiryAug 14, 2028(~2.1 yrs left)· nominal 20-yr term from priority
G16B 40/00G16B 25/00
56
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Claims
Abstract
Methods, software, and systems are provided for determining the probability of an overlap set of entities having an overlap size, where the overlap set is independently selected from two sets of non-identical entities. Applications of the invention to microarrays are provided. Probability distributions are provided for determining the probability that the size of an overlap gene set from two different microarrays occurs by chance. Microarray analysis for determining the size of a statistically significant overlap gene set given two different microarrays is described. Overlap set size probability determinations that account for the total number of genes in two different microarrays and not just the common genes are described.
Claims
exact text as granted — not AI-modified1 . A computer-implemented method for determining the suitability of a therapeutic treatment from microarray expression data, comprising:
selecting a first gene set of interest, wherein the first gene set of interest is expressed in a first gene expression microarray of a first subject being treated for a first disorder; selecting a second gene set of interest, wherein the second gene set of interest is expressed in a second gene expression microarray of a second subject, wherein the second subject has a second disorder, and wherein the first microarray and the second microarray are functionally linked to a computer system comprising an input/output device capable of receiving data from a microarray reader, wherein the computer system comprises a processor; determining a size of an overlap gene set between the first gene set and the second gene set, and employing the processor to determine whether the overlap gene set is significant by determining the probability that the overlap gene set size is drawn by chance from the total number of genes of each microarray; wherein determining the probability that the overlap gene set size is drawn by chance comprises determining a function of the total number of ways of selecting a gene set having the same size as the first gene set from all genes of the first microarray and comprises determining a function of the total number of ways of selecting a gene set having the same size as the second gene set from all genes of the second microarray; and wherein determining that the overlap gene set is significant indicates that a therapeutic treatment effective against the first disorder is suitable for treatment of the second disorder.
2 . A method according to claim 1 , wherein the probability that the overlap set size is selected by chance comprises determining the number of ways of selecting any overlap set size from all genes common to both the first microarray and the second microarray to obtain a first numeral, and dividing the first numeral by:
(a) the number of ways of selecting a gene set having the same size as the first gene set from the first microarray expression data, multiplied by (b) the number of ways of selecting a gene set having the same size as the second gene set from the second microarray expression data.
3 . A method according to claim 2 , wherein the number of ways of selecting any overlap set size from all genes common to both the first microarray and the second microarray is multiplied by a sum, over the minimum of either
(a′) the number of genes of a first subset of genes of the first microarray that are not common with a second subset of genes of the second microarray, or (b′) the number of genes common between the first and second microarrays, excluding the number of genes common between the first and the second subsets of genes, of: (a″) the number of ways of choosing a number of genes in the first subset of genes that are included in the second microarray but are not included in the overlap set, from the number of common genes between the two microarrays excluding the overlap set, multiplied by, (b″) the number of ways of choosing a number of genes in the first subset of genes that are not included in the second microarray, from the number of genes in the first microarray excluding genes common with the second microarray, multiplied by, (c″) the number of ways of choosing a number of genes in that part of the second subset of genes that are not in the overlap set, from the genes in the second microarray excluding those genes in the first subset of genes.
4 . A method according to claim 1 , wherein the overlap probability is determined by the formula
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wherein
X is the number of genes in the first microarray;
Y is the number of genes in the second microarray;
M represents the number of genes common to both the first microarray and the second microarray; m is the number of genes in the overlap set; x is the number of genes of the first gene set; y is the number of genes of the second gene set; and, p(m) is the probability of selecting the overlap set of size m by chance.
5 . A computer-implemented method according to claim 1 , wherein the first and second array differ by at least 1% but less than 10% of the total number of genes of the first and second array.
6 . A computer-implemented method according to claim 1 , wherein he first and second array differ by at least 10% but less than 20% of the total number of genes of the first and second array.
7 . A computer-implemented method according to claim 1 , wherein the first and second array differ by at least 20% but less than 30% of the total number of genes of the first and second array.
8 . A computer-implemented method according to claim 1 , wherein the first and second array differ by at least 30% but less than 40% of the total number of genes of the first and second array.
9 . A computer-implemented method according to claim 1 , wherein the first and second array differ by at least 40% but less than 50% of the total number of genes of the first and second array.
10 . A computer product comprising a computer-readable medium encoded with a computer program containing computer-implementable instructions for carrying out a determination of the probability that an overlap gene set is drawn by chance as defined in any one of claims 1 to 4 .
11 . A system comprising:
(a) a processor; and, (b) memory coupled with the processor, wherein the memory stores a plurality of computer-implementable instructions that cause the processor to carry out a determination of the probability that an overlap gene set is drawn by chance as defined in any one of claims 1 to 4 .Cited by (0)
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