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...
| Main Authors: | , , , |
|---|---|
| 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 |
| _version_ | 1819239567329329152 |
|---|---|
| author | Johannes M Freudenberg Ian Dunham Philippe Sanseau Deepak K Rajpal |
| author_facet | Johannes M Freudenberg Ian Dunham Philippe Sanseau Deepak K Rajpal |
| author_sort | Johannes M Freudenberg |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T13:54:10Z |
| format | Article |
| id | doaj.art-7215bd07903a4fc9a32ae54218ef2001 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-23T13:54:10Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-7215bd07903a4fc9a32ae54218ef20012022-12-21T17:44:31ZengBMCBMC 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 |
| 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 |
| title | 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_short | 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 |
| topic | G-protein coupled receptors Drug discovery Data integration Target identification |
| url | http://link.springer.com/article/10.1186/s12859-018-2392-y |
| work_keys_str_mv | AT johannesmfreudenberg uncoveringnewdiseaseindicationsforgproteincoupledreceptorsandtheirendogenousligands AT iandunham uncoveringnewdiseaseindicationsforgproteincoupledreceptorsandtheirendogenousligands AT philippesanseau uncoveringnewdiseaseindicationsforgproteincoupledreceptorsandtheirendogenousligands AT deepakkrajpal uncoveringnewdiseaseindicationsforgproteincoupledreceptorsandtheirendogenousligands |