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

Journal: Nucleic acids research
Published Date: Jan 8, 2021

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.

Authors

  • David Ochoa
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Andrew Hercules
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Miguel Carmona
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Daniel Suveges
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Asier Gonzalez-Uriarte
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Cinzia Malangone
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Alfredo Miranda
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Luca Fumis
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Denise Carvalho-Silva
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Michaela Spitzer
    Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, UK; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8N 3Z5, Canada.
  • Jarrod Baker
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Javier Ferrer
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Arwa Raies
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Olesya Razuvayevskaya
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Adam Faulconbridge
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Eirini Petsalaki
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Prudence Mutowo
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Sandra Machlitt-Northen
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Gareth Peat
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Elaine McAuley
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Chuang Kee Ong
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Edward Mountjoy
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Maya Ghoussaini
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Andrea Pierleoni
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Eliseo Papa
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Miguel Pignatelli
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Gautier Koscielny
    Centre for Therapeutic Target Validation, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD UK ; GSK, Medicine Research Centre, Stevenage, SG1 2NY UK.
  • Mohd Karim
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Jeremy Schwartzentruber
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • David G Hulcoop
    Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Ian Dunham
    European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD UK ; Centre for Therapeutic Target Validation, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD UK.
  • Ellen M McDonagh
    European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.

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