Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines

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...

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Main Authors: Chhibber, A, French, C E, Yee, S W, Gamazon, E R, Theusch, E, Qin, X, Webb, A, Papp, A C, Wang, A, Simmons, C Q, Konkashbaev, A, Chaudhry, A S, Mitchel, K, Stryke, D, Ferrin, T E, Weiss, S T, Kroetz, D L, Sadee, W, Nickerson, D A, Krauss, R M, George, A L, Schuetz, E G, Medina, M W, Cox, N J, Scherer, S E, Giacomini, K M, Brenner, S E
Format: Online
Language:English
Published: Nature Publishing Group 2017
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980276/
id pubmed-4980276
recordtype oai_dc
spelling pubmed-49802762017-03-24 Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines Chhibber, A French, C E Yee, S W Gamazon, E R Theusch, E Qin, X Webb, A Papp, A C Wang, A Simmons, C Q Konkashbaev, A Chaudhry, A S Mitchel, K Stryke, D Ferrin, T E Weiss, S T Kroetz, D L Sadee, W Nickerson, D A Krauss, R M George, A L Schuetz, E G Medina, M W Cox, N J Scherer, S E Giacomini, K M Brenner, S E Original Article 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. Nature Publishing Group 2017-03 2016-02-09 /pmc/articles/PMC4980276/ /pubmed/26856248 http://dx.doi.org/10.1038/tpj.2015.93 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chhibber, A
French, C E
Yee, S W
Gamazon, E R
Theusch, E
Qin, X
Webb, A
Papp, A C
Wang, A
Simmons, C Q
Konkashbaev, A
Chaudhry, A S
Mitchel, K
Stryke, D
Ferrin, T E
Weiss, S T
Kroetz, D L
Sadee, W
Nickerson, D A
Krauss, R M
George, A L
Schuetz, E G
Medina, M W
Cox, N J
Scherer, S E
Giacomini, K M
Brenner, S E
spellingShingle Chhibber, A
French, C E
Yee, S W
Gamazon, E R
Theusch, E
Qin, X
Webb, A
Papp, A C
Wang, A
Simmons, C Q
Konkashbaev, A
Chaudhry, A S
Mitchel, K
Stryke, D
Ferrin, T E
Weiss, S T
Kroetz, D L
Sadee, W
Nickerson, D A
Krauss, R M
George, A L
Schuetz, E G
Medina, M W
Cox, N J
Scherer, S E
Giacomini, K M
Brenner, S E
Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
author_facet Chhibber, A
French, C E
Yee, S W
Gamazon, E R
Theusch, E
Qin, X
Webb, A
Papp, A C
Wang, A
Simmons, C Q
Konkashbaev, A
Chaudhry, A S
Mitchel, K
Stryke, D
Ferrin, T E
Weiss, S T
Kroetz, D L
Sadee, W
Nickerson, D A
Krauss, R M
George, A L
Schuetz, E G
Medina, M W
Cox, N J
Scherer, S E
Giacomini, K M
Brenner, S E
author_sort Chhibber, A
title Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
title_short Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
title_full Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
title_fullStr Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
title_full_unstemmed Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
title_sort transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
description 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.
publisher Nature Publishing Group
publishDate 2017
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980276/
_version_ 1613625224116305920

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