Benchmarking of sequencing technologies defines optimal strategies for genetic variants detection in a human genome

作者：Robert J. M. Eveleigh, Sarah Julia Reiling, José Héctor Gálvez, Mathieu Bourgey, Jiannis Ragoussis, Guillaume Bourque · 发表于：Genome biology · 年份：2026 · DOI：10.1186/s13059-026-04048-4 · 被引用次数：3 · 研究领域：Genomics and Rare Diseases、Genomics and Phylogenetic Studies、Cancer Genomics and Diagnostics

BACKGROUND: Advances in sequencing technologies continue to improve the resolution and completeness with which human genetic variation can be characterized. Short-read sequencing remains widely used due to its high base accuracy, throughput, and cost efficiency; however, its limited ability to resolve repetitive and structurally complex regions has accelerated adoption of long-read sequencing platforms, including those from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT). RESULTS: We systematically compared sequencing technologies and variant calling pipelines for small variants and structural variants across diverse genomic contexts and sequencing depths. Short-read sequencing combined with DRAGEN achieved high accuracy for single-nucleotide variants (SNVs) and indels in well-mapped and moderately complex regions but showed reduced sensitivity and completeness for structural variant detection. In contrast, long-read sequencing platforms demonstrated clear advantages in detecting structural variants and resolving small variants in difficult genomic regions, although challenges remain in specific indel-prone sequence contexts. Among long-read pipelines, PacBio Revio with DeepVariant achieved the highest SNV and indel accuracy genome-wide, while ONT R10 with DeepVariant performed particularly well in clinically relevant loci. Structural variant detection was dominated by long-read optimized callers, with SVIM and Sawfish performing best for PacBio, and Sniff...