VSPGx: A High-Accuracy Pharmacogenomics Interpretation Software Solution with Automated CPIC Guideline Integration

Accurate pharmacogenomic genotype determination and interpretation are essential for personalized medicine, yet existing bioinformatics tools face significant limitations in detecting named alleles, maintaining current allele definitions, and providing comprehensive clinical annotations. We present VSPGx, a pharmacogenomics interpretation software solution that identifies diplotypes from next-generation sequencing data and annotates them against Clinical Pharmacogenetics Implementation Consortium (CPIC) and FDA drug recommendations using automated curation of the latest allele definitions.

We benchmarked VSPGx against established tools including Aldy, PharmCAT, and Stargazer using both synthetic datasets and real-world clinical samples. In a comprehensive synthetic benchmark spanning 3,655 CYP2C9 diplotype combinations, VSPGx achieved 99.97% concordance, matching PharmCAT’s performance and substantially outperforming Aldy (93.08%) and Stargazer (27.06%). Clinical validation using 11 TaqMan OpenArray samples demonstrated 88.2% allele concordance and 89.1% phenotype concordance across 110 gene-sample combinations, with all discrepancies attributed to the benchmark data utilizing outdated allele definitions rather than VSPGx errors. Our automated curation process ensures continuous alignment with current CPIC guidelines, addressing a critical gap in existing pharmacogenomic analysis tools. VSPGx provides a robust, clinically-validated solution for pharmacogenomic analysis that combines high-accuracy diplotype calling with up-to-date, evidence-based drug recommendations.