Comprehensive characterization of somatic alterations of cancer genomes on personalized diploid reference genomes using tumor and matched normal cell-line samples
Detecting somatic variants in highly repetitive and individual-specific regions, such as centromeres, telomeres, and segmental duplications, remains challenging with standard human reference genomes. Personalized diploid reference genomes built from matched normal samples by de novo assembly can address this. However, a comprehensive framework bringing the major classes of somatic alterations together on the same personalized reference genome has been lacking. To develop and evaluate such a framework, we collected whole-genome sequencing data from tumor and matched normal cell lines using multiple platforms, including PacBio HiFi and Oxford Nanopore ultra-long reads, Illumina short reads, and Hi-C data.