HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data

Matthew A. Myers, Brian J. Arnold, Vineet Bansal, Metin Balaban, Katelyn M. Mullen, Simone Zaccaria, Benjamin J. Raphael

Research output: Contribution to journalArticlepeer-review

Abstract

Bulk DNA sequencing of multiple samples from the same tumor is becoming common, yet most methods to infer copy-number aberrations (CNAs) from this data analyze individual samples independently. We introduce HATCHet2, an algorithm to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 extends the earlier HATCHet method by improving identification of focal CNAs and introducing a novel statistic, the minor haplotype B-allele frequency (mhBAF), that enables identification of mirrored-subclonal CNAs. We demonstrate HATCHet2’s improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 10 prostate cancer patients reveals previously unreported mirrored-subclonal CNAs affecting cancer genes.

Original languageEnglish (US)
Article number130
JournalGenome biology
Volume25
Issue number1
DOIs
StatePublished - Dec 2024

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Keywords

  • Allele-specific
  • Cancer
  • Clone
  • Copy-number aberrations
  • DNA sequencing
  • Genomics
  • Haplotype
  • Tumor heterogeneity

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