Guardant Health, Inc.
METHODS AND SYSTEMS FOR DIFFERENTIATING SOMATIC AND GERMLINE VARIANTS

Abstract:

In an aspect, a method of identifying a somatic or germline origin of a nucleic acid variant from a sample of nucleic acid molecules comprises: determining quantitative measures for the nucleic acid variant comprising total allele count and minor allele count for the nucleic acid variant; identifying an associated variable of the nucleic acid variant; determining quantitative value for the associated variable; generating a statistical model for expected germline mutant allele counts at a genomic locus of the nucleic acid variant; generating a probability value (p-value) for the nucleic acid variant based at least in part on the statistical model, the quantitative value, and at least one of the quantitative measures; and classifying the nucleic acid variant as (i) being of somatic origin when the p-value is below a predetermined threshold value, or as (ii) being of germline origin when the p-value is at or above the predetermined threshold value.