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

• Published in: Clinical and translational science Vol. 11; no. 2; pp. 153 - 161
• Main Authors: Sá, Ana Caroline C., Sadee, Wolfgang, Johnson, Julie A.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2018; John Wiley and Sons Inc
• Subjects: Antihypertensives; Disease; DNA microarrays; Gene expression; Genes; Genomes; Genomics; Heterogeneity; Identification; Oligonucleotides; Pharmacogenomics; Phenotypes; Precision medicine; Proteins; Regulators; Ribonucleic acid; RNA; Single-nucleotide polymorphism; Splicing; Studies; Transcription; Tutorial
• ISSN: 1752-8054; 1752-8062
• DOI: 10.1111/cts.12511

[...]enhanced understanding of gene expression patterns can lead to molecular pathways that underlie disease susceptibility or drug response. The power of sequencing RNA vs. using oligonucleotides to assess gene expression with microarrays lies in the fact that both transcript discovery and quantification can be incorporated in one high‐throughput sequencing assay with RNA‐Seq. [...]RNA‐Seq enables dynamic assessment of mechanisms associated with disease and drug response to bridge the gap between genomics and phenotype, providing a powerful tool germane to precision medicine. [...]integration of the BP signature genes, eQTLs, and GWAS results revealed that six SNPs associated with BP (P < 5 × 10−8 in the ICBP GWAS ) are also trans regulators of several top BP signature genes. [...]this study provides important avenues for future investigation on the impact of these transcriptomic markers to predict antihypertensive drug response, and serves as an example of the insights to be gained from RNA Seq data—insights that are valuable alone, and amplified when coupled with GWAS data. Gene expression variation and the diversity of splicing events occurring in drug‐metabolizing enzymes, drug transporters, and drug targets have been associated with heterogeneity in drug response and adverse drug events. [...]a comprehensive study of the potential variability on transcriptome profiling associated with pharmacogenomics phenotypes can provide relevant insights into the molecular basis of heterogeneity in drug response.