biostudies-literaturePaulin LFNIDA NIH HHSNHGRI NIH HHSNINDS NIH HHSNIH621-631https://www.ebi.ac.uk/biostudies/studies/S-EPMC12047239biostudies-literatureUnknown35(4)The complexities of cancer genomes are becoming more easily interpreted due to advancements in sequencing technologies and improved bioinformatic analysis. Structural variants (SVs) represent an important subset of somatic events in tumors. While the detection of SVs has been markedly improved by the development of long-read sequencing, somatic variant identification and annotation remain challenging. We hypothesized that the use of a completed human reference genome (CHM13-T2T) would improve somatic SV calling. Our findings in a tumor-normal matched benchmark sample and three patient samples show that the CHM13-T2T improves SV detection accuracy compared to GRCh38 with a notable reduction in false-positive calls, and thus supports improved prioritization. We also overcame the lack of annoGenome researchClosing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T.PMC120472391UG3NS132105-011U01HG011758-01UG3 NS132105U01 HG011758UM1DA058229UM1 DA058229O'Neill KSedlazeck FJFan JJones SJMPorter VLPleasance EPaulin LFfalseClosing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T.The complexities of cancer genomes are becoming more easily interpreted due to advancements in sequencing technologies and improved bioinformatic analysis. Structural variants (SVs) represent an important subset of somatic events in tumors. While the detection of SVs has been markedly improved by the development of long-read sequencing, somatic variant identification and annotation remain challenging. We hypothesized that the use of a completed human reference genome (CHM13-T2T) would improve somatic SV calling. Our findings in a tumor-normal matched benchmark sample and three patient samples show that the CHM13-T2T improves SV detection accuracy compared to GRCh38 with a notable reduction in false-positive calls, and thus supports improved prioritization. We also overcame the lack of anno2025-01-01T00:00:00Z2025 Apr2026-06-03T23:30:31.342Z2026-05-03T03:11:26.457ZS-EPMC120472394009720010.1101/gr.279352.124