Literature evidence in open targets - a target validation platform

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

doi:10.1186/s13326-017-0131-3

Cited by 19 publications

(17 citation statements)

References 17 publications

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“…Document confidence scores for a given target-disease association are calculated by assigning different weights to the paper sections (such as Title, Abstract, Results, etc.) and are used in the target validation platform to rank all the documents relevant to a given target-disease association (34). …”

Section: The Open Targets Target Validation Platformmentioning

confidence: 99%

Open Targets: a platform for therapeutic target identification and validation

et al. 2016

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We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

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Section: The Open Targets Target Validation Platformmentioning

confidence: 99%

Open Targets: a platform for therapeutic target identification and validation

et al. 2016

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“…As has been observed elsewhere [ 18 ], the number of gene-disease pairs with a positive score varies considerably between the different data types. For example, 46% of the pairs had a literature mining score greater than zero compared to less than 5% of pairs with somatic mutation, known drugs, or affected pathways scores greater than zero, respectively (Fig.…”

Section: Resultsmentioning

confidence: 63%

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

et al. 2018

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BackgroundThe 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.ResultsUtilizing 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2392-y) contains supplementary material, which is available to authorized users.

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“…OA targets were collected from the Open Targets Platform ( https://www.targetvalidation.org ) [ 17 ], which is a comprehensive and authoritative database for screening and visualizing potential drug targets related to diseases. It brings together a variety of data types designed to help users identify and prioritize targets for further research [ 18 ]. We used the keyword “osteoarthritis” in the Open Targets Platform.…”

Section: Methodsmentioning

confidence: 99%

A Systematic Pharmacology and In Vitro Study to Identify the Role of the Active Compounds of Achyranthes bidentata in the Treatment of Osteoarthritis

Chen

Zheng

2020

Med Sci Monit

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Backgrounds Achyranthes bidentata is a Chinese traditional herbal medicine widely used to treat osteoarthritis (OA) . This study aimed to identify active compounds from Achyranthes bidentata through systematic pharmacology and in vitro experiments to find the targets of Achyranthes bidentata in the treatment of OA. Material/Methods We screened the active compounds of Achyranthes bidentata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Then, we used STITCH and Open Targets Platform databases to screen the active components and predict the potential targets of Achyranthes bidentata in the treatment of OA. Subsequently, we studied the compound-target network and protein interaction network and analyzed the enrichment of potential target proteins. Finally, we used Western blot analysis to verify the therapeutic effect of Achyranthes bidentata extract on the expression of OA-related target proteins. Results There were 7 active components in Achyranthes bidentata , which were strongly related to the 74 targets of OA. Quercetin, baicalein, and berberine are the critical active compounds of Achyranthes bidentata in the treatment of OA. Protein interaction analysis and in vitro experiments suggested that TNF, IL-6, and TP53 are the critical targets of Achyranthes bidentata in the treatment of OA. Functional enrichment analysis showed that Achyranthes bidentata plays a pharmacological role in OA through apoptosis, inflammation, and immune regulation. Conclusions Quercetin, baicalein, and berberine are the critical active compounds of Achyranthes bidentata in the treatment of OA. TNF, IL-6, and TP53 may be potential targets for the treatment of OA.

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Literature evidence in open targets - a target validation platform

Cited by 19 publications

References 17 publications

Open Targets: a platform for therapeutic target identification and validation

Open Targets: a platform for therapeutic target identification and validation

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

A Systematic Pharmacology and In Vitro Study to Identify the Role of the Active Compounds of Achyranthes bidentata in the Treatment of Osteoarthritis

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