An efficient genotyper and star-allele caller for pharmacogenomics.

TitleAn efficient genotyper and star-allele caller for pharmacogenomics.
Publication TypeJournal Article
Year of Publication2023
AuthorsHari, A, Zhou, Q, Gonzaludo, N, Harting, J, Scott, SA, Qin, X, Scherer, SE, S Sahinalp, C, Numanagić, I
JournalGenome Res
Date Published2023 Jan
KeywordsAlleles, Genomics, Genotype, High-Throughput Nucleotide Sequencing, Humans, Pharmacogenetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA

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.

Alternate JournalGenome Res
PubMed ID36657977
PubMed Central IDPMC9977157

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