公开(公告)号：US20200075124A1

公开(公告)日：2020-03-05

申请号：US16560752

申请日：2019-09-04

Applicant: GUARDANT HEALTH, INC.

Inventor： Jing Zhao ,  Stephen FAIRCLOUGH ,  Tracy NANCE ,  Jie YIN

IPC: G16B20/20 ,  C12Q1/6827 ,  G16B30/20 ,  G16B30/10 ,  G16B50/30

Abstract: The present disclosure provides methods and systems for detecting an allelic imbalance in a sample from a subject, comprising: (a) sequencing cell-free DNA molecules from the sample to generate sequence reads; (b) aligning at least a portion of the sequence reads to a reference sequence to produce aligned sequence reads; (c) for at least a portion of the plurality of aligned sequence reads, identifying a germline variant present at a mutant allele fraction (MAF) in the sample, thereby identifying a set of germline variants in the sample, wherein individual germline variants in the set of germline variants have corresponding MAF values; (d) determining a quantitative measure of the set of germline variants that are among a plurality of discrete ranges of MAF values; and (e) detecting the allelic imbalance based on a predetermined criterion by filtering the set of germline variants based on at least the quantitative measure.

公开(公告)号：US20200327954A1

公开(公告)日：2020-10-15

申请号：US16823937

申请日：2020-03-19

Applicant: GUARDANT HEALTH, INC.

Inventor： Tracy NANCE ,  Elena HELMAN ,  Darya CHUDOVA

IPC: G16B5/00 ,  G06F17/18 ,  C12P19/34 ,  C12Q1/6869

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.