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

Autor:	Holt JM; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Harting J; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Chen X; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Baker D; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Saunders CT; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Kronenberg Z; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Gonzaludo N; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA., Yoo B; Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA., Hudjashov G; Estonian Genome Centre, Institute of Genomics, University of Tartu, Estonia., Jõeloo M; Estonian Genome Centre, Institute of Genomics, University of Tartu, Estonia., Lawlor JMJ; HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA., Lim WK; SingHealth Duke-NUS Institute of Precision Medicine, 5 Hospital Drive, Singapore 169609, Singapore.; Cancer & Stem Cell Biology Program, Duke-NUS Medical School, Singapore, 169857, Singapore.; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore., Jamuar SS; SingHealth Duke-NUS Institute of Precision Medicine, 5 Hospital Drive, Singapore 169609, Singapore.; Genetics service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899., Cooper GM; HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA., Milani L; Estonian Genome Centre, Institute of Genomics, University of Tartu, Estonia., Pastinen T; Children's Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA., Eberle MA; PacBio, 1305 O'Brien Drive, Menlo Park, CA 94025, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Dec 11. Date of Electronic Publication: 2024 Dec 11.
DOI:	10.1101/2024.12.10.627527
Abstrakt:	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.
Databáze:	MEDLINE
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