Copy number variant caller
AssigneeMyriad Women's Health, Inc.
InventorsKevin R. Haas, Xin Wang, Peter V. Grauman
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Abstract
Direct targeted sequencing (DTS) methods and a hidden Markov model (HMV) can be used to call the copy number of a segment of interest within a region of interest. Described herein are methods for calling a copy number variant or a copy number variant abnormality using an HMM, and methods for determining a copy number based on a copy number likelihood model, in a test sequencing library that has be sequenced using DTS methods. Also described herein are methods for determining a copy number of a segment, including accounting for spurious capture probes that may arise from the DTS methods.
Claims13
A system for determining a copy number of an interrogated segment of nucleic acids within a region of interest of a genome, the system comprising a non-transitory computer-readable storage medium programed to:
- (a) obtain a plurality of sequencing reads from a test sequencing library
- (b) map the plurality of sequencing reads with the interrogated segment;
- and
- (c) determine the copy number of the interrogated segment,
- wherein the copy number is the most probable copy number of the interrogated segment as determined by an optimized parameterized hidden Markov model comprising:
- (i) one or more hidden states comprising a copy number corresponding to the interrogated segment or a plurality of sub-segments within the interrogated segment;
- (ii) an observation state comprising a number of sequencing reads mapped to the interrogated segment;
- and
- (iii) a copy number likelihood model using one or more likelihood distributions for an expected number of sequencing reads mapped to the interrogated segment,
- wherein the hidden Markov model is parameterized by adjusting the copy number likelihood model to fit the determined number of sequencing reads mapped to the interrogated segment by allowing portions of the likelihood distributions to float.
Dependencies are inferred from the claim text.