ArticleScientific reports2025
Preliminary evaluation of ShallowHRD performance compared to HRDetect in familial breast cancer tumors.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
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11 authors.
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Abstract
Determining the Homologous Recombination Deficiency (HRD)-status of a malignant tumor is central in predicting patient response to specific treatments. Therefore, precise and cost-effective tools are needed for clinical implementation. HRDetect is widely regarded as a golden standard for determining HRD-status. In contrast, ShallowHRD is a simpler algorithm. However, it offers a more economical alternative optimized for Formalin-Fixed, Paraffin-Embedded tissue (FFPE) and potentially useful for most breast cancer patients. Data from shallow whole-genome sequencing (1-5X) on FFPE tissue and whole-genome sequencing (50X, and additionally downscaled to 5X) on fresh frozen tissue from 19 patients were analyzed using ShallowHRD and compared to the HRD-status attained by HRDetect using Receiver Operating Characteristic (ROC) curve analysis. Further, Spearman rank correlation was calculated to estimate the correlation between ShallowHRD and HRDetect scores, as well as between the three ShallowHRD datasets. The comparison of ShallowHRD to HRDetect displayed a significant specificity (85.7-100%) and sensitivity (80%) in all data groups. The ROC curve analyses illustrated that ShallowHRD displayed an area under the curve statistically similar to what was previously reported for HRDetect in all three data sets. The Spearman correlation also indicated significant correlation between ShallowHRD and HRDetect scores for the three datasets (HRDetect vs. FFPE (1-5X) (ρ = 0.68, p = 0.0013), Fresh Frozen (5X) (ρ = 0.58, p = 0.0086), and Fresh Frozen (50X) (ρ = 0.50, p = 0.029)). The ShallowHRD analysis was of good quality in all data groups, and the ShallowHRD scores were similar across data groups. One sample was incorrectly labeled as HRD-negative by ShallowHRD, but it contained one variant of unknown significance (VUS) in RAD51D, requiring further investigation. HRD-status from ShallowHRD correlated well with HRDetect output in this preliminary study, potentially making ShallowHRD an accurate, efficient, and more economical alternative for clinical use. However, further examination and validation in larger cohorts are required.
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