Reduction of next-generation sequencing files for efficient pharmacogenotype extraction.

Abstract

Objectives: The most comprehensive computational pharmacogenotype extraction methods utilize Binary Alignment/Map (BAM) files, which require intensive storage resources. The pharmacogenotyping tool Aldy, which has been validated using clinical whole exome (ES) and whole genome sequencing (GS), can also extract genotypes from targeted DNA sequencing. Our objectives were to (1) assess Aldy's genotype extraction accuracy for 14 major pharmacogenes from clinical ES and GS BAMs that were reduced to only contain pharmacogene regions and (2) determine the amount of computational storage resources saved.

Patients and methods: Germline ES (n = 160) and GS (n = 94) BAMs were reduced to contain only pharmacogene regions. Aldy was used to extract genotypes for 14 major phamacogenes from both full and reduced BAM files, and results and file sizes were compared.

Results: All genotype calls from reduced ES and GS BAMs were concordant with those from full BAMs. Reducing files to only contain pharmacogene regions decreased mean ES and GS BAM sizes from 9,707 megabytes (MB) to 7.6 MB and from 107,353 MB to 51.8 MB, respectively.

Conclusions: This analysis demonstrates Aldy's ability to accurately extract pharmacogenotypes from reduced BAM files, decreasing required storage resources by >1,000-fold.