Patent ID: 8200440

Claim:
A method for determining the genotype of a plurality of nucleic acid samples at a plurality of SNPs, comprising: (a) hybridizing each nucleic acid sample in said plurality of nucleic acid samples to an array of allele specific probes to obtain a plurality of raw probe intensity measurements; (b) normalizing said raw probe intensity measurements to obtain normalized probe intensities; (c) summarizing the normalized probe intensities to obtain an allele signal estimate for each allele of each SNP in each nucleic acid sample, wherein the allele signal estimate for each allele of each SNP in each nucleic acid sample comprises a first value S A and a second value S B where S A is the summary value for a first allele of the SNP and S B is the summary value for a second allele of the SNP; (d) transforming said allele signal estimates in clustering space in one-dimension to obtain a transformed allele signal estimate for each SNP in each nucleic acid sample using the following equation: transformed allele signal estimate =asinh(K(S A −S B )/(S A +S B ))/asinh(K), where K is a tuning constant; (e) obtaining a prior distribution of genotype cluster characteristics; (f) evaluating all possible assignments of the transformed allele signal estimates to the genotype clusters of the prior distribution; (g) calculating an optimal assignment from the possible assignments of step (f) for each transformed allele signal estimate, to one or more genotype clusters using a Gaussian cluster model; (h) updating the prior distribution with optimal assignments calculated in (g) to obtain a posterior distribution of genotype cluster characteristics for each SNP; and (i) using the posterior distribution of genotype cluster characteristics for each SNP to make genotype calls for that SNP in each nucleic acid sample.