Guardant Health, Inc.
COMPUTATIONAL DETECTION OF COPY NUMBER VARIATION AT A LOCUS IN THE ABSENCE OF DIRECT MEASUREMENT OF THE LOCUS

Abstract:

Methods and systems are described for improving detection of copy number loss of a locus of interest without requiring direct measurement of the locus of interest. The locus of interest may include the human leukocyte antigen (HLA) locus, for which copy number loss is implicated in cancer. Direct measurement of the HLA locus, which is on human chromosome 6, may be unavailable due to the polymorphic nature of the HLA. Thus, the system may infer the genetic state of the HLA locus. For example, the system may generate and use a probabilistic ML model that determines a probability that a given sample of a subject has a copy number loss at the HLA locus based on copy number determinations of segments of chromosome 6 that are determined to be predictive of copy number loss at the HLA locus.