Dataset Information

Open Targets Platform: supporting systematic drug-target identification and prioritisation.

ABSTRACT: The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integrated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive.

SUBMITTER: Ochoa D

PROVIDER: S-EPMC7779013 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Open Targets Platform: supporting systematic drug-target identification and prioritisation.

Ochoa David D Hercules Andrew A Carmona Miguel M Suveges Daniel D Gonzalez-Uriarte Asier A Malangone Cinzia C Miranda Alfredo A Fumis Luca L Carvalho-Silva Denise D Spitzer Michaela M Baker Jarrod J Ferrer Javier J Raies Arwa A Razuvayevskaya Olesya O Faulconbridge Adam A Petsalaki Eirini E Mutowo Prudence P Machlitt-Northen Sandra S Peat Gareth G McAuley Elaine E Ong Chuang Kee CK Mountjoy Edward E Ghoussaini Maya M Pierleoni Andrea A Papa Eliseo E Pignatelli Miguel M Koscielny Gautier G Karim Mohd M Schwartzentruber Jeremy J Hulcoop David G DG Dunham Ian I McDonagh Ellen M EM

Nucleic acids research 20210101 D1

The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integ ...[more]

PMID: 33196847

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Project description:BackgroundHuman schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma that still affects some 200 million people. The mainstay of schistosomiasis control is a single drug, praziquantel. The reliance on this drug carries a risk of resistance emerging to this anthelmintic, such that research towards alternative anti-schistosomal drugs is warranted. In this context, a number of studies have employed computational approaches to prioritise proteins for investigation as drug targets, based on extensive genomic, transcriptomic and small-molecule data now available.MethodsHere, we established a customisable, online application for the prioritisation of drug targets and applied it, for the first time, to the entire inferred proteome of S. haematobium. This application enables selection of weighted and ranked proteins representing potential drug targets, and integrates transcriptional data, orthology and gene essentiality information as well as drug-drug target associations and chemical properties of predicted ligands.ResultsUsing this application, we defined 25 potential drug targets in S. haematobium that associated with approved drugs, and 3402 targets that (although they could not be linked to any compounds) are conserved among a range of socioeconomically important flatworm species and might represent targets for new trematocides.ConclusionsThe online application developed here represents an interactive, customisable, expandable and reproducible drug target ranking and prioritisation approach that should be useful for the prediction of drug targets in schistosomes and other species of parasitic worms in the future. We have demonstrated the utility of this online application by predicting potential drug targets in S. haematobium that can now be evaluated using functional genomics tools and/or small molecules, to establish whether they are indeed essential for parasite survival, and to assist in the discovery of novel anti-schistosomal compounds.

Dataset Information

Open Targets Platform: supporting systematic drug-target identification and prioritisation.

Publications

Open Targets Platform: supporting systematic drug-target identification and prioritisation.

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