Genotyping sequence-resolved copy number variation using pangenomes reveals paralog-specific global diversity and expression divergence of duplicated genes.

ABSTRACT: Copy number variant (CNV) genes are important in evolution and disease, yet sequence variation in CNV genes remains a blind spot in large-scale studies. We present ctyper, a method that leverages pangenomes to produce allele-specific copy numbers with locally phased variants from next-generation sequencing (NGS) reads. Benchmarking on 3,351 CNV genes, including HLA, SMN, and CYP2D6, and 212 challenging medically relevant (CMR) genes that are poorly mapped by NGS, ctyper captures 96.5% of phased variants with ≥99.1% correctness of copy number on CNV genes and 94.8% of phased variants on CMR genes. Applying alignment-free algorithms, ctyper requires 1.5 hours per genome on a single CPU. The results largely improve predictions of gene expression compared to known expressi

SUBMITTER: Ma W 

PROVIDER: S-EPMC11326217 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature