An efficient genotyper and star-allele caller for pharmacogenomics.
Ananth HariQinghui ZhouNina GonzaludoJohn HartingStuart A ScottXiang QinSteve SchererS Cenk SahinalpIbrahim NumanagićPublished in: Genome research (2023)
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.
Keyphrases
- copy number
- genome wide
- mitochondrial dna
- single cell
- dna methylation
- high throughput sequencing
- high throughput
- end stage renal disease
- high resolution
- healthcare
- ejection fraction
- chronic kidney disease
- newly diagnosed
- prognostic factors
- gene expression
- emergency department
- cancer therapy
- mass spectrometry
- drug delivery
- single molecule
- drug induced
- genome wide identification
- patient reported