1. Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.
- Author
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Chhibber A, French CE, Yee SW, Gamazon ER, Theusch E, Qin X, Webb A, Papp AC, Wang A, Simmons CQ, Konkashbaev A, Chaudhry AS, Mitchel K, Stryke D, Ferrin TE, Weiss ST, Kroetz DL, Sadee W, Nickerson DA, Krauss RM, George AL, Schuetz EG, Medina MW, Cox NJ, Scherer SE, Giacomini KM, and Brenner SE
- Subjects
- Adipose Tissue metabolism, Cell Line, Databases, Genetic, Genotype, Humans, Kidney metabolism, Liver metabolism, Myocardium metabolism, Phenotype, Alternative Splicing, Computational Biology, High-Throughput Nucleotide Sequencing, Pharmacogenetics, Pharmacogenomic Variants, Sequence Analysis, RNA, Transcriptome
- Abstract
Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.
- Published
- 2017
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