Systems and methods for tumor fraction estimation from small variants

Abstract

Systems and methods for cancer subject tumor fraction estimation comprise obtaining a first plurality of nucleic acid fragment sequences from the subject's liquid biological sample. The first plurality of sequences represent cell-free nucleic acids in the liquid sample. A second plurality of nucleic acid fragment sequences is obtained from the subject's tumor sample. The second plurality of sequences represent nucleic acid molecules in the tumor. Smoothed noise rates, each determined using nucleic acid fragment sequences from non-cancer samples mapping to a corresponding allele position in a plurality of allele positions, are obtained. Variant allele counts and coverages are determined for the allele positions using the first plurality of sequences. Solid variant allele fractions are determined for the plurality of allele positions using the second plurality of sequences. The subject tumor fraction is calculated using the smoothed noise rates, variant allele counts, coverages, and solid variant allele fractions.