Benchmarking copy number variation detection with low-coverage whole-genome sequencing.

ABSTRACT: Low-coverage whole-genome sequencing (lcWGS) provides a cost-effective method for genome-wide copy number variation (CNV) profiling, yet its technical limitations and analytical variability require systematic evaluation. We benchmarked five CNV detection tools using simulated and real-world datasets, focusing on sequencing depth, formalin-fixed paraffin-embedded (FFPE) artifacts, tumor purity, multi-center reproducibility, and signature-level stability. Our results demonstrate that ichorCNA outperformed other tools in precision and runtime at high purity (≥50%), making it the optimal choice for lcWGS-based workflows. Prolonged FFPE fixation induced artifactual short-segment CNVs due to formalin-driven DNA fragmentation, a bias none of the tools could computationally correct, necessitating

SUBMITTER: Wang N 

PROVIDER: S-EPMC12481693 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature