Holt James M, Harting John, Chen Xiao, Baker Daniel, Saunders Christopher T, Kronenberg Zev, Gonzaludo Nina, Yoo Byunggil, Hudjashov Georgi, Jõeloo Maarja, Lawlor James M J, Lim Weng Khong, Jamuar Saumya S, Cooper Gregory M, Milani Lili, Pastinen Tomi, Eberle Michael A
PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA.
Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA.
bioRxiv. 2024 Dec 11:2024.12.10.627527. doi: 10.1101/2024.12.10.627527.
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 , , and . 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.
药物基因组学是精准医学的核心，为药物安全性和有效性提供依据。对复杂基因进行药物基因组双倍型分析需要全长DNA序列并检测结构重排。我们引入了StarPhase工具，该工具利用PacBio HiFi序列数据对21个临床药物基因组学实施联盟（CPIC）A级药物基因进行双倍型分析，并为[此处原文缺失具体基因名称]提供详细的单倍型和支持性可视化结果。StarPhase双倍型与基准高度一致，其中99.5%要么是完全匹配，要么是微小差异。对0.5%的不匹配进行人工检查表明，它们被StarPhase正确识别。使用StarPhase，我们更新或纠正了26.2%的GeT-RM药物基因组双倍型。StarPhase的群体分布大多反映了“我们所有人”队列的分布情况，同时也凸显了现有药物基因组数据库中长读长测序可以填补的空白。通过单次HiFi全基因组测序分析，即使发现了更多的药物基因和单倍型，StarPhase也能实现可靠的药物基因组学双倍型分析。
