RT Journal
A1 Hari, Ananth
A1 Zhou, Qinghui
A1 Gonzaludo, Nina
A1 Harting, John
A1 Scott, Stuart A.
A1 Qin, Xiang
A1 Scherer, Steve
A1 Sahinalp, S. Cenk
A1 Numanagić, Ibrahim
T1 An efficient genotyper and star-allele caller for pharmacogenomics
JF Genome Research 
JO Genome Research 
YR 2023 
FD January 01 
VO 33 
IS 1 
SP 61 
OP 70 
DO 10.1101/gr.277075.122 
UL http://genome.cshlp.org/content/33/1/61.abstract 
AB 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.