Clinical Validation of a 106-SNV MALDI-ToF MS Pharmacogenomic Panel. (30th April 2020)

• Record Type: Journal Article
• Authors: Williams, Grace R; Cook, Leanne; Lewis, Lionel D; Tsongalis, Gregory J; Nerenz, Robert D
• Is Part Of: Journal of applied laboratory medicine. Volume 5:Number 3(2020)
• Page Start: 454
• Page End: 466
• Publication Date: 2020-04-30
• Subjects: PGX74 -- MALDI-ToF MS -- Pharmacogenomics -- SNV -- SNP -- MassARRAY; Clinical chemistry -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.0756
• DOI: 10.1093/jalm/jfaa018
• Languages: English
• ISSNs: 2576-9456

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.