DirectHRD enables sensitive scar-based classification of homologous recombination deficiency.

ABSTRACT: Homologous recombination deficiency (HRD) is a predictive biomarker for efficacy of PARP (poly ADP-ribose polymerase) inhibition and platinum chemotherapy for cancer patients but remains challenging to detect. The discovery of patients without pathogenic mutations in known HR genes but exhibiting genomic scars indicative of HRD led to the FDA approval of the first scar-based HRD test. Despite advancements in whole genome sequencing (WGS) and integration of large training datasets with machine learning models, current methods lack the sensitivity required for detecting HRD scars in low tumor purity samples, especially in liquid biopsies. Here, we describe DirectHRD, a genomic scar-based HRD classifier based on WGS. Compared to other WGS-based methods, DirectHRD exclusively utilizes a highly

SUBMITTER: Liu R 

PROVIDER: S-EPMC12014287 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature