Tempus Labs, Inc.

Justin David Finkle

Robert Tell

Wei Zhu

Terri M Driessen

Christine Lo

Methods, systems, and software are provided for validating a somatic sequence variant in a subject having a cancer condition. Sequence reads are obtained from sequencing cell-free DNA fragments in a liquid biopsy sample of the subject. Sequence reads are aligned to a reference sequence. A variant allele fragment count and locus fragment count are identified for a candidate variant that maps to a locus in the reference sequence. The variant allele fragment count is compared against a dynamic variant count threshold for the locus. The threshold is based on a pre-test odds of a positive variant call for the locus, based on the prevalence of variants in a genomic region including the locus in a cohort of subjects having the cancer condition. The somatic sequence variant in the subject is validated, or rejected, when the variant allele fragment count for the candidate variant satisfies, or does not satisfy, the threshold.

Methods and systems for dynamic variant thresholding in a liquid biopsy assay

Methods, systems, and software are provided for estimating a circulating tumor fraction for a test subject. Sequence reads are obtained from a panel-enriched sequencing reaction, including sequences for a first plurality of cfDNA fragments corresponding to probe sequences and a second plurality of cfDNA fragments not corresponding to probe sequences. Bin-level coverage ratios are determined from the sequences. Segments are formed by grouping adjacent bins based on similar coverage ratios and segment-level coverage ratios are determined based on bin-level coverage ratios for bins in the segment. For each simulated circulating tumor fraction in a plurality of circulating tumor fractions, segments are fitted to an integer copy state by identifying the integer copy state that best matches the segment-level coverage ratio. The circulating tumor fraction for the test subject is determined using error optimization between segment-level coverage ratios and integer copy states across the simulated circulated tumor fractions.

Growing community of inventors

Chicago, IL, United States of America

Justin David Finkle