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Updated: Jul 21, 2025

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data
Matthew A Myers1, Brian J Arnold2, Vineet Bansal3
1Department of Computer Science, Princeton University, Princeton, USA.
Abstract:
Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce HATCHet2 to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 introduces a novel statistic, the mirrored haplotype B-allele frequency (mhBAF), to identify mirrored-subclonal CNAs having different numbers of copies of parental haplotypes in different tumor clones. HATCHet2 also has high accuracy in identifying focal CNAs and extends the earlier HATCHet method in several directions. We demonstrate HATCHet2's improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 50 prostate cancer samples from 10 patients reveals previously-unreported mirrored-subclonal CNAs affecting cancer genes.
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