2025/10/28 by Qian Qin, Jakob Heinz, Heng Li · 1 voice
Biochemistry, Genetics and Molecular Biology · #Cancer Genomics and Diagnostics #Genomics and Rare Diseases #Genomics and Phylogenetic Studies
paper · pdf · doi:10.1101/2025.10.28.685154
openalex publication_date 2025/10/28 · openalex created_date 2025/10/29 · openalex updated_date 2026/07/22
Accurate detection of mosaic and somatic structural variants (SVs) provides early diagnostic and therapeutic evidence for cancers. While long-read whole-genome sequencing leads to more accurate SV detection than short read sequencing, existing long-read SV callers only look at alignment against a single reference genome and are susceptible to systematic false discovery caused by germline differences between the individual genome and the reference genome. Here we develop a new SV calling method that jointly considers the alignment against a pangenome and the de novo assembly of the germline genome. It dramatically reduces false positive mosaic SVs in normal samples and somatic SVs in cancer cell lines with little loss in sensitivity. Our study highlights the essential need for pangenome or personal genome assembly to integrate SV calls for both SV discoveries and clinical diagnostics.