An efficient genotyper and star-allele caller for pharmacogenomics

Ananth Hari, Qinghui Zhou, Nina Gonzaludo, John Harting, Stuart A. Scott, Xiang Qin, Steve Scherer, S. Cenk Sahinalp, Ibrahim Numanagic

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation identification, variant calling, and phasing within each pharmacogene copy present in the sample. Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that uses combinatorial optimization for accurate star-allele calling across different sequencing technologies. Aldy 4 adds support for long reads and uses a novel phasing model and improved copy number and variant calling models. We compare Aldy 4 against the current state-of-the-art star-allele callers on a large and diverse set of samples and genes sequenced by various sequencing technologies, such as whole-genome and targeted Illumina sequencing, barcoded 10x Genomics, and Pacific Biosciences (PacBio) HiFi. We show that Aldy 4 is the most accurate star-allele caller with near-perfect accuracy in all evaluated contexts, and hope that Aldy remains an invaluable tool in the clinical toolbox even with the advent of long-read sequencing technologies.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalGenome Research
Volume33
Issue number1
DOIs
StatePublished - Jan 2023
Externally publishedYes

Fingerprint

Dive into the research topics of 'An efficient genotyper and star-allele caller for pharmacogenomics'. Together they form a unique fingerprint.

Cite this