World class research today, superior patient care tomorrow
As recognized leaders in pharmacogenomics (PGx), Dr. Broeckel and the RPRD research team are known for their scientific rigor and academic excellence. We partner with the world’s leading medical institutions to advance PGx research and practice.
View our academic publications and scientific contributions listed below that highlight our academic excellence and commitments in scientific and clinical research.
Performance Analysis of a Comprehensive Clinically Focused Pharmacogenetic Assay
Pharmacogenomics Research Network (PGRN) Meeting 2020
INTRODUCTION: Genotyping of relevant pharmacogenetic (PGx) genes and HLA typing for known associations with drug metabolism and hypersensitivity allows for personalized drug selection and dosing prior to administration. The accuracy and reproducibility of testing methodologies are critical to ensure accurate phenotype assignment. We have previously demonstrated the quality and relevance of the PharmacoScan™ (pScan) assay for clinical PGx testing. While pScan offers the most comprehensive genotyping platform (4,627 ADME markers in 1,191 genes + copy number analysis) there continues to be a need for a more targeted, higher throughput and more cost-effective platforms. In this study we tested the PharmacoFocus™ (pFocus) assay, a targeted assay (2,000+ ADME markers in 150 genes + copy number analysis) that includes highly relevant PGx genes and markers and offers the potential for routine and reliable clinical PGx testing.
METHODS: Genomic DNA (gDNA) was acquired from Coriell (isolated from LCL cell lines) or isolated from Liver, blood, buccal and saliva. Samples were batched (including mixed sample types per plate) and run using the PharmacoScan™ Assay Kit (pScan), 24-Format or the PharmacoFocusTM Assay Kit (pFocus), 96-Format. Array analysis was done using the Axiom™ Analysis Suite and performance of each assay was determined by calculating both inter- and intra-run specificity, sensitivity, and concordance.
RESULTS: There are 8,416 probes that are used for genotyping on the pFocus assay. To test the quality of probes, the per sample genotypes were compared for all the probes. 99.6% of the probes showed high inter-run concordance. On a sample level, all samples genotyped on pFocus showed a passing QC call rate >98%. The intra- and inter-run concordance for all the samples run on pFocus was >99%. The intra-run concordance metrics include samples from different gDNA sources. When comparing the pScan and pFocus assays, >8,000 genotyping probes were used. On the probe level, all samples demonstrated >99.5% concordance between the two assays. The star allele haplotype concordance was >99.3% for the relevant PGx genes. All samples on both assays showed 100% concordance with copy number qPCR results for CYP2D6, including CYP2D6/CYP2D7 hybrids.
CONCLUSIONS: We evaluated the pFocus assay, a more targeted array-based platform derived from pScan. PharmacoFocus, includes the most clinically relevant and actionable PGx genes and markers. The intra- and inter-run results demonstrate that despite the reduced content on pFocus, the quality of the genotypes is highly accurate and reproducible. We also show that the assay performs well for gDNA samples derived from different source types. The more targeted scope of pFocus makes it a high throughput and cost-effective clinical testing platform to complement the strength of the pScan assay, which lies in a broader scope of clinical, research and in certain cases discovery-based testing.
Pharmacogenomic Genotyping Performance Across Biological Specimens
Presented at the University of Minnesota Biennial Pharmacogenomics Conference 2020
Turner, A., Aggarwal, P., Scharer, G., Derezenski, A., Gaedigk, A., Broeckel, U.
Drs. Broeckel (CEO and founder) and Scharer (CMO) are both long-standing members of the CPIC® since its inception in 2009. CPIC is a pioneering PGx consortium committed to facilitating the implementation of PGx testing in the clinic by providing actionable clinical guidelines to translate genetic tests results into customized patient-focused prescribing decisions by physicians for certain drugs. The detailed evidence-based, gene/drug clinical recommendations created by CPIC are peer-reviewed and are being increasingly used in the clinical practice. They are regarded as the standard guideline in PGx clinical implementation.
Amy Turner (Director of Research and Development) is a member of the Pharmacogene Variation (PharmVar) Consortium and serves as a gene expert for CYP2D6, NUDT15, and DPYD.
PharmVar was established in 2018 and funded by the Pharmacogenomics Research Network (PGRN) to serve as repository for PGx gene data and its nomenclature. PharmVar aims to facilitate and develop a standardized PGx gene nomenclature for the entire global PGx community.
Amy Turner’s contribution to the PharmVar NUDT15 gene introduction:
Genetic Testing Reference Materials Coordination Program (GeT-RM)
Dr. Broeckel and his research team have been an important contributor to the GeT-RM since 2015. As part of the Clinical Laboratory Improvement Amendments (CLIA) regulations of 1988, the Get-RM program is supported by the Centers for Disease Control and Prevention (CDC). The goal of the GeT-RM is to establish a PGx community dedicated to creating reference materials, quality control measures, and proficiency testing for genetic testing.
Dr. Broeckel’s team has characterized the PGx impact of genomic DNA reference materials utilizing the PharmacoScanTM and its predecessor DMET platform.
As a team primarily driven by passion for science, we are excited to work with the bright minds in the precision medicine community. If you are interested in collaborating with RPRD, please contact us to discuss potential opportunities.
Improve Drug R&D
Pharmacogenetics testing is an increasingly important tool to mitigate risks for clinical trials, interpretation of clinical data and retrospective studies.