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Review
. 2019 Jun;40(6):378-387.
doi: 10.1016/j.tips.2019.04.001. Epub 2019 May 8.

GPCRomics: An Approach to Discover GPCR Drug Targets

Paul A Insel  1 , Krishna Sriram  2 , Matthew W Gorr  2 , Shu Z Wiley  2 , Alexander Michkov  2 , Cristina Salmerón  2 , Amy M Chinn  3
Affiliations
Review

GPCRomics: An Approach to Discover GPCR Drug Targets

Paul A Insel et al. Trends Pharmacol Sci. 2019 Jun.

Abstract

G protein-coupled receptors (GPCRs) are targets for ∼35% of approved drugs but only ∼15% of the ∼800 human GPCRs are currently such targets. GPCRomics, the use of unbiased, hypothesis-generating methods [e.g., RNA-sequencing (RNA-seq)], with tissues and cell types to identify and quantify GPCR expression, has led to the discovery of previously unrecognized GPCRs that contribute to functional responses and pathophysiology and that may be therapeutic targets. The combination of GPCR expression data with validation studies (e.g., signaling and functional activities) provides opportunities for the discovery of disease-relevant GPCR targets and therapeutics. Here, we review insights from GPCRomic approaches, gaps in knowledge, and future directions by which GPCRomics can advance GPCR biology and the discovery of new GPCR-targeted drugs.

Keywords: G protein-coupled receptors (GPCRs); G proteins; RNA-sequencing; cancer-associated fibroblasts; cyclic AMP; gene expression.

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Figures

Figure 1,
Figure 1,. Key Figure.
Evaluation of GPCR mRNA expression in biological samples, such as primary cells or tissues, relies on isolation of high-quality RNA, i.e. with minimal protein and DNA contamination and minimal degradation. High-throughput methods, such as RNA-seq, then identify and quantify GPCRs. This GPCR expression data forms the basis for further studies to validate the expression of GPCRs via independent mRNA and protein analyses, cell signaling and functional assays, use of animal models and human genetic analyses. Abbreviations used: NGS: next-generation sequencing, TG = transgenic; KD/KO = Knockdown/Knockout
Figure 2:
Figure 2:. RNA-sequencing and data analysis for GPCRomics.
The schematic describes a workflow and tools for analyzing RNA-seq raw-data that yields gene (GPCR) expression data together with output that includes analyses of differential expression (DE), enrichment of GPCRs and mRNAs involved in GPCR-regulated signaling and response.
See this image and copyright information in PMC

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