ABSTRACT Homologous recombination deficiency (HRD) guides PARP inhibitor and platinum‐based therapy selection but relies on costly next‐generation sequencing with limited accessibility. Here, we show that IHGAMP, a computational framework using vision transformer foundation models, predicts HRD from routine H PTRC‐HGSOC platinum resistance AUROC 0.673), with attenuation in squamous histologies. True external validation using the frozen TCGA‐trained model on CPTAC‐LUAD yielded AUROC 0.671, confirming cross‐institutional generalization. Pathway specificity analysis demonstrated that the apparent TP53 correlation was mediated through HRD (partial r = 0.112 after controlling for scarHRD), and evaluation on MMR‐deficient endometrial carcinoma yielded below‐random prediction (AUC = 0.445), ruling out general genomic instability capture. Sensitivity analysis across label definitions (scarHRD ≥ 33 and ≥ 42) showed robust performance, and a BRCA1/2 mutation‐trained comparator performed near‐randomly (AUC = 0.486), confirming that learned features reflect HRD biology beyond single‐gene effects. IHGAMP supports a screening/triage role to prioritize confirmatory molecular testing where appropriate.
Zafar et al. (2026) studied this question.