DirectHRD enables sensitive scar-based classification of homologous recombination deficiency (HRD)

Ruolin Liu; Eugenia Roberts; Heather Anne Parsons; Elizabeth H. Stover; Atish Dipankar Choudhury; Justin Rhoades; Timothy Blewett; David Dewei Yang; Joyce F. Liu; Erica L. Mayer; Viktor A. Adalsteinsson

doi:10.1093/nar/gkaf313

BioinformaticsNucleic Acids ResearchApr 17, 2025

Peer-reviewed journal article

DirectHRD enables sensitive scar-based classification of homologous recombination deficiency (HRD)

Ruolin Liu iD, Eugenia Roberts iD, Heather Anne Parsons iD, Elizabeth H. Stover iD, Atish Dipankar Choudhury iD, Justin Rhoades iD, Timothy Blewett iD, David Dewei Yang iD, Joyce F. Liu iD, Erica L. Mayer iD, Viktor A. Adalsteinsson iD

Abstract

Homologous recombination deficiency (HRD) is a predictive biomarker for efficacy of PARP inhibition and platinum chemotherapy but remains challenging to detect from low tumor fraction samples such as liquid biopsies. Here, we describe DirectHRD, a whole-genome sequencing (WGS) scar-based classifier that is 10x more sensitive than state-of-the-art methods. DirectHRD can detect HRD at >=1% tumor fraction using 50x WGS of cell-free DNA.

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