HATCHet2: Clone- and Haplotype-specific Copy Number Inference from Bulk Tumor Sequencing Data

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2024 May 21

PMID 38773520

Authors

Matthew A Myers

Brian J Arnold

Vineet Bansal

Metin Balaban

Katelyn M Mullen

Simone Zaccaria

Benjamin J Raphael

Affiliations

Soon will be listed here.

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.

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