Complete pharmacogenomic profile from exome sequencing

Exome sequencing (ES) is a cornerstone of clinical genetic diagnosis, yet its application in pharmacogenomics remains limited. While some pharmacogenetic variants are detectable by ES, clinically relevant loci such as CYP2D6, UGT1A1, and HLA remain challenging. We present a robust, comprehensive method to derive a complete pharmacogenomic profile directly from standard ES data. Our method addresses primary limitations of ES for pharmacogenomics, including low coverage and structural complexity at critical loci. We analyzed 66 samples from diverse sources, targeting 217 variants across a panel of 23 pharmacogenes. The method was validated by comparing its results with reference samples from the Genetic Testing Reference Material Coordination Program, as well as with the Veridose Core+CNV assay(R) (Agena) and the Personal Medicine Profile assay(R) (GeneTelligence). HLA typing performance was assessed and confirmed through comparison with both the Immucor LIFECODES HLA-SSO kit and a clinical transplantation-grade HLA assay. This validation demonstrates that ES can provide a comprehensive pharmacogenomic profile in a single, streamlined workflow, facilitating seamless integration of pharmacogenomics into precision medicine.