Copy number variant caller
AssigneeMyriad Genetics, Inc.
InventorsKevin R. Haas, Xin Wang, Peter V. Grauman
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Abstract
Direct targeted sequencing (DTS) methods and a hidden Markov model (HMM) 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.
Claims27
A method for determining a copy number of an interrogated segment of nucleic acids within a region of interest of a genome, comprising:
- (a) mapping a plurality of sequencing reads of nucleic acids generated from a test sequencing library to the interrogated segment;
- (b) determining a number of sequencing reads mapped to the interrogated segment;
- (c) determining a copy number likelihood model using a plurality of likelihood distributions associated with an expected number of sequencing reads mapped to the interrogated segment;
- (d) building a 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 the number of sequencing reads mapped to the interrogated segment;
- and
- (iii) the copy number likelihood model;
- (e) parameterizing the hidden Markov model 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;
- and
- (f) determining a most probable copy number of the interrogated segment by optimizing the parameterized hidden Markov model.
Dependencies are inferred from the claim text.