Whole Transcriptome Profiling: An RNA‐Seq Primer and Implications for Pharmacogenomics Research

Pharmacogenomics has revealed compelling genetic signals associated with variability in drug response. Gene expression studies represent an additional approach to identify candidate genes accounting for drug response variability. This review focuses on insights that might be gained through analysis of the transcriptome to reveal the influence of gene expression on variable drug response. We provide a basic overview of RNA-Sequencing (RNA-Seq) and its applications, and outline advances in pharmacogenomics achievable with RNA-Seq data. This article is protected by copyright. All rights reserved

• Publication year

  2017

• Venue

  Clinical and Translational Science

• Publication date

  2017-10-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/cts.12511PMID 28945944PMCID 5866981
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2016influential reference
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  2015cited by this paper
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• Pre-mRNA splicing in disease and therapeutics.

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• The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity

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• Genomics and drug response.

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• From DNA to diversity: molecular genetics and the evolution of animal design (2nd ed.)

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• Genetics of global gene expression

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• Heritability and Tissue Specificity of Expression Quantitative Trait Loci

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• Genetic interactions between polymorphisms that affect gene expression in yeast

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