Abstract 2042: A next-generation sequencing-based sample-to-result pharmacogenomics research solution enables both SNV and CNV detection at once
Authors: Wei Melvin S. , Chen Zhoutao , Chen Shann-Ching , Manivannan Manimozhi , Zeringer Emily , Patel Sunali , Hartshorne Toinette , Liu Guoying , Hyland Fiona , Andersen Mark 
Published: July 2016

Abstract
Pharmacogenomics (PGx) is the study of genetic variations in terms of their response to drugs. Variations in gene sequence or copy number may result in complete loss of function, partial decrease or increase in enzyme activity, or an altered affinity for substrates, which may in turn significantly impact a drug's efficacy. PGx studies are increasing in significance as precision medicine is becoming a reality in standard practice. Different technologies have been developed to measure the sequence variation and copy number variation (CNV) in the PGx genes. Among them, a complete sample-to-result PGx workflow solution using the QuantStudio™ 12k Flex Real-Time PCR System is the most notable high throughput solution and has broad adoption by advanced PGx laboratories. Both PGx SNP/INDEL genotyping assays on OpenArray™ plates and copy number analysis on 384-well plates can be performed on the QuantStudio™ 12k Flex System. Integrated analysis software translates genotyping and copy number assay results into star allele genotypes for ease of interpretation. Recently we have developed a next generation sequencing (NGS) based PGx research solution with increased flexibility on the assay targets and combined detection of SNP/INDEL genotyping and CNV using Ion AmpliSeq™ technology for low to medium throughput laboratories. With a highly multiplexed PGx research panel, we can profile a set of 136 genetic markers in 40 known PGx related genes and CYP2D6 copy number variation in a single reaction using Ion Torrent™ semiconductor sequencing. The number of genetic markers can be customized easily based on the user need. To systematically compare these two end-to-end PGx workflows, we collected buccal swab samples from 20 individuals and performed both QuantStudio™ based assays and PGM™ based Ion AmpliSeq™ PGx research assay on them. Both systems generated high quality results. Compared with OpenArray™ plate genotyping results and 384-plate CYP2D6 copy number assay results from the QuantStudio™ system, the Ion AmpliSeq™ PGx research solution demonstrated &gt;99.9% genotyping concordance, 100% CYP2D6 gene CNV concordance, &gt;99.7% reproducibility, &lt;0.2% no-call rate. The Ion AmpliSeq™ PGx solution enables flexible and integrated SNV & CNV detection for both standard genotyping practice and sophisticated exploratory research needs.
Citation Format: Melvin S. Wei, Zhoutao Chen, Shann-Ching Chen, Manimozhi Manivannan, Emily Zeringer, Sunali Patel, Toinette Hartshorne, Guoying Liu, Fiona Hyland, Mark Andersen. A next-generation sequencing-based sample-to-result pharmacogenomics research solution enables both SNV and CNV detection at once. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2042.