FocalSV: target region-based structural variant assembly and refinement using single-molecule long read sequencing data

Abstract

Structural variants (SVs) play a critical role in shaping the diversity of the human genome and their detection holds significant potential for advancing precision medicine. Despite notable progress in single-molecule long-read sequencing technologies, accurately identifying SV breakpoints and resolving their sequence remains a major challenge. Current alignment-based tools often struggle with precise breakpoint detection and sequence characterization, while whole genome assembly-based methods are computationally demanding and less practical for targeted analyses. Neither approach is ideally suited for scenarios where regions of interest are predefined and require precise SV characterization. To address this gap, we introduce FocalSV, a target region assembly-based SV detection tool that combines the precision of assembly-based methods with the efficiency of region-specific approaches. FocalSV was evaluated on nine germline datasets and two paired normal-tumor cancer datasets, demonstrating superior performance in both precision and efficiency.