Clinical Validation of a 106-SNV MALDI-ToF MS Pharmacogenomic Panel

Abstract

Abstract Background Laboratorians have the opportunity to help minimize the frequency of adverse drug reactions by implementing pharmacogenomic testing and alerting care providers to possible patient/drug incompatibilities before drug treatment is initiated. Methods combining PCR with MALDI-ToF MS have allowed for sensitive, economical, and multiplexed pharmacogenomic testing results to be delivered in a timely fashion. Method This study evaluated the analytical performance of the Agena Biosciences iPLEX® PGx 74 panel and a custom iPLEX panel on a MassARRAY MALDI-TOF MS instrument in a clinical laboratory setting. Collectively, these panels evaluate 112 SNVs across 34 genes implicated in drug response. Using commercially available samples (Coriell Biorepository) and in-house extracted DNA, we determined ideal reaction conditions and assessed accuracy, precision, and robustness. Results Following protocol optimization, the Agena PGx74 and custom panels demonstrated 100% concordance with the 1000 Genomes Project Database and clinically validated hydrolysis probe genotyping assays. 100% concordance was also observed in all assessments of assay precision when appropriate QC metrics were applied. Conclusions Significant development time was required to optimize sample preparation and instrumental analysis and 3 assays were removed due to inconsistent performance. Following modification of the manufacturer’s protocol and instituting manual review of each assay plate, the Agena PGx74 and custom panel constitute a cost-effective, robust, and accurate method for clinical identification of 106 SNVs involved in drug response.