StarPhase: Comprehensive Phase-Aware Pharmacogenomic Diplotyper for Long-Read Sequencing Data

作者：James Holt, John Harting, Xiao Chen, Daniel N. Baker, Christopher T. Saunders, Zev Kronenberg, Nina Gonzaludo, Byunggil Yoo, Georgi Hudjashov, Maarja Jõeloo, James M.J. Lawlor, Weng Khong Lim, Saumya Shekhar Jamuar, Gregory M. Cooper, Lili Milani, Tomi Pastinen, Michael A. Eberle · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.12.10.627527 · 被引用次数：9 · 研究领域：Glycosylation and Glycoproteins Research、T-cell and B-cell Immunology、Single-cell and spatial transcriptomics

Pharmacogenomics is central to precision medicine, informing medication safety and efficacy. Pharmacogenomic diplotyping of complex genes requires full-length DNA sequences and detection of structural rearrangements. We introduce StarPhase, a tool that leverages PacBio HiFi sequence data to diplotype 21 CPIC Level A pharmacogenes and provides detailed haplotypes and supporting visualizations for HLA-A, HLA-B, and CYP2D6. StarPhase diplotypes have high concordance with benchmarks where 99.5% are either exact matches or minor discrepancies. Manual inspection of the 0.5% mismatches indicates they were correctly called by StarPhase. With StarPhase, we update or correct 26.2% of GeT-RM pharmacogenomic diplotypes. Population distributions from StarPhase mostly reflect those of the All of Us cohort, while also highlighting gaps in existing pharmacogenomic databases that long-read sequencing can fill. With a single HiFi whole genome sequencing assay, StarPhase enables robust PGx diplotyping even as additional pharmacogenes and haplotypes are discovered.