Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands

Abstract Background The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases. It currently provides evidence for nearly 2.6 million potential target-disease pairs. G-protein coupled receptors are a...

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Main Authors: Johannes M Freudenberg, Ian Dunham, Philippe Sanseau, Deepak K Rajpal
Format: Article
Language:English
Published: BMC 2018-10-01
Series:BMC Bioinformatics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12859-018-2392-y
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spelling doaj-7215bd07903a4fc9a32ae54218ef20012020-11-24T20:46:37ZengBMCBMC Bioinformatics1471-21052018-10-0119111110.1186/s12859-018-2392-yUncovering new disease indications for G-protein coupled receptors and their endogenous ligandsJohannes M Freudenberg0Ian Dunham1Philippe Sanseau2Deepak K Rajpal3Computational Biology, Target Sciences, GlaxoSmithKlineOpen Targets, Wellcome Genome CampusOpen Targets, Wellcome Genome CampusComputational Biology, Target Sciences, GlaxoSmithKlineAbstract Background The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases. It currently provides evidence for nearly 2.6 million potential target-disease pairs. G-protein coupled receptors are a drug target class of high interest because of the number of successful drugs being developed against them over many years. Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands. Results Utilizing the data available in the Open Targets platform, potential G-protein coupled receptor and endogenous ligand disease association pairs were systematically identified. Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for viral infection are used as illustrations of how a systematic approach can aid in the prioritization of interesting drug discovery hypotheses. Combining evidences for G-protein coupled receptors and their corresponding endogenous peptidergic ligands increases confidence and provides supportive evidence for potential new target-disease hypotheses. Comparing such hypotheses to the global pharma drug discovery pipeline to validate the approach showed that more than 93% of G-protein coupled receptor-disease pairs with a high overall Open Targets score involved receptors with an existing drug discovery program. Conclusions The Open Targets gene-disease score can be used to prioritize potential G-protein coupled receptors-indication hypotheses. In addition, availability of multiple different evidence types markedly increases confidence as does combining evidence from known receptor-ligand pairs. Comparing the top-ranked hypotheses to the current global pharma pipeline serves validation of our approach and identifies and prioritizes new therapeutic opportunities.http://link.springer.com/article/10.1186/s12859-018-2392-yG-protein coupled receptorsDrug discoveryData integrationTarget identification
collection DOAJ
language English
format Article
sources DOAJ
author Johannes M Freudenberg
Ian Dunham
Philippe Sanseau
Deepak K Rajpal
spellingShingle Johannes M Freudenberg
Ian Dunham
Philippe Sanseau
Deepak K Rajpal
Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
BMC Bioinformatics
G-protein coupled receptors
Drug discovery
Data integration
Target identification
author_facet Johannes M Freudenberg
Ian Dunham
Philippe Sanseau
Deepak K Rajpal
author_sort Johannes M Freudenberg
title Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
title_short Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
title_full Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
title_fullStr Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
title_full_unstemmed Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands
title_sort uncovering new disease indications for g-protein coupled receptors and their endogenous ligands
publisher BMC
series BMC Bioinformatics
issn 1471-2105
publishDate 2018-10-01
description Abstract Background The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases. It currently provides evidence for nearly 2.6 million potential target-disease pairs. G-protein coupled receptors are a drug target class of high interest because of the number of successful drugs being developed against them over many years. Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands. Results Utilizing the data available in the Open Targets platform, potential G-protein coupled receptor and endogenous ligand disease association pairs were systematically identified. Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for viral infection are used as illustrations of how a systematic approach can aid in the prioritization of interesting drug discovery hypotheses. Combining evidences for G-protein coupled receptors and their corresponding endogenous peptidergic ligands increases confidence and provides supportive evidence for potential new target-disease hypotheses. Comparing such hypotheses to the global pharma drug discovery pipeline to validate the approach showed that more than 93% of G-protein coupled receptor-disease pairs with a high overall Open Targets score involved receptors with an existing drug discovery program. Conclusions The Open Targets gene-disease score can be used to prioritize potential G-protein coupled receptors-indication hypotheses. In addition, availability of multiple different evidence types markedly increases confidence as does combining evidence from known receptor-ligand pairs. Comparing the top-ranked hypotheses to the current global pharma pipeline serves validation of our approach and identifies and prioritizes new therapeutic opportunities.
topic G-protein coupled receptors
Drug discovery
Data integration
Target identification
url http://link.springer.com/article/10.1186/s12859-018-2392-y
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