Optimized summation test based on nested t-tests that maximize separation between carriers and non-carriers

Abstract

A computer-implemented method for performing an optimized summation test for a particular gene, wherein an optimal combination of maximum allele count and minimum pathogenicity score threshold (862) that maximizes the significance of the summation test for rare deleterious variants is determined using a grid search (822) protocol. Each combination of maximum allele count and minimum pathogenicity score threshold is tested (824) with a t-test to obtain an effect size and p-value (842). The combination of allele count and pathogenicity score threshold with the most significant p-value (842) is selected as the optimal parameter for the rare deleterious variant summation test for the particular gene.

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