TY  - JOUR
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
Y1  - 2023/01/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 61 
EP  - 70 
DO  - 10.1101/gr.277075.122 
VL  - 33 
IS  - 1 
UR  - http://genome.cshlp.org/content/33/1/61.abstract 
N2  - 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. 
ER  -