Literature DB >> 33196847

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

David Ochoa1,2, Andrew Hercules1,2, Miguel Carmona1,2, Daniel Suveges1,2, Asier Gonzalez-Uriarte1,2, Cinzia Malangone1,2, Alfredo Miranda1,2, Luca Fumis1,2, Denise Carvalho-Silva1,2, Michaela Spitzer1,2, Jarrod Baker1,2, Javier Ferrer1,2, Arwa Raies1,2, Olesya Razuvayevskaya1,2, Adam Faulconbridge1,2, Eirini Petsalaki1,2, Prudence Mutowo2,3, Sandra Machlitt-Northen2,3, Gareth Peat1,2, Elaine McAuley1,2, Chuang Kee Ong1,2, Edward Mountjoy2,4, Maya Ghoussaini2,4, Andrea Pierleoni1,2, Eliseo Papa2,5, Miguel Pignatelli1,2, Gautier Koscielny2,3, Mohd Karim2,4, Jeremy Schwartzentruber2,4, David G Hulcoop2,3, Ian Dunham1,2,4, Ellen M McDonagh1,2.   

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.
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

Entities:  

Year:  2021        PMID: 33196847      PMCID: PMC7779013          DOI: 10.1093/nar/gkaa1027

Source DB:  PubMed          Journal:  Nucleic Acids Res        ISSN: 0305-1048            Impact factor:   16.971


  40 in total

1.  Modeling sample variables with an Experimental Factor Ontology.

Authors:  James Malone; Ele Holloway; Tomasz Adamusiak; Misha Kapushesky; Jie Zheng; Nikolay Kolesnikov; Anna Zhukova; Alvis Brazma; Helen Parkinson
Journal:  Bioinformatics       Date:  2010-03-03       Impact factor: 6.937

2.  The support of human genetic evidence for approved drug indications.

Authors:  Matthew R Nelson; Hannah Tipney; Jeffery L Painter; Judong Shen; Paola Nicoletti; Yufeng Shen; Aris Floratos; Pak Chung Sham; Mulin Jun Li; Junwen Wang; Lon R Cardon; John C Whittaker; Philippe Sanseau
Journal:  Nat Genet       Date:  2015-06-29       Impact factor: 38.330

Review 3.  Approaches to target tractability assessment - a practical perspective.

Authors:  Kristin K Brown; Michael M Hann; Ami S Lakdawala; Rita Santos; Pamela J Thomas; Kieran Todd
Journal:  Medchemcomm       Date:  2018-02-14       Impact factor: 3.597

4.  A genetics-led approach defines the drug target landscape of 30 immune-related traits.

Authors:  Hai Fang; Hans De Wolf; Bogdan Knezevic; Katie L Burnham; Julie Osgood; Anna Sanniti; Alicia Lledó Lara; Silva Kasela; Stephane De Cesco; Jörg K Wegner; Lahiru Handunnetthi; Fiona E McCann; Liye Chen; Takuya Sekine; Paul E Brennan; Brian D Marsden; David Damerell; Chris A O'Callaghan; Chas Bountra; Paul Bowness; Yvonne Sundström; Lili Milani; Louise Berg; Hinrich W Göhlmann; Pieter J Peeters; Benjamin P Fairfax; Michael Sundström; Julian C Knight
Journal:  Nat Genet       Date:  2019-06-28       Impact factor: 38.330

5.  Pharos: Collating protein information to shed light on the druggable genome.

Authors:  Dac-Trung Nguyen; Stephen Mathias; Cristian Bologa; Soren Brunak; Nicolas Fernandez; Anna Gaulton; Anne Hersey; Jayme Holmes; Lars Juhl Jensen; Anneli Karlsson; Guixia Liu; Avi Ma'ayan; Geetha Mandava; Subramani Mani; Saurabh Mehta; John Overington; Juhee Patel; Andrew D Rouillard; Stephan Schürer; Timothy Sheils; Anton Simeonov; Larry A Sklar; Noel Southall; Oleg Ursu; Dusica Vidovic; Anna Waller; Jeremy Yang; Ajit Jadhav; Tudor I Oprea; Rajarshi Guha
Journal:  Nucleic Acids Res       Date:  2016-11-29       Impact factor: 16.971

6.  Deconvoluting Kinase Inhibitor Induced Cardiotoxicity.

Authors:  Sarah D Lamore; Ernst Ahlberg; Scott Boyer; Michelle L Lamb; Maria P Hortigon-Vinagre; Victor Rodriguez; Godfrey L Smith; Johanna Sagemark; Lars Carlsson; Stephanie M Bates; Allison L Choy; Jonna Stålring; Clay W Scott; Matthew F Peters
Journal:  Toxicol Sci       Date:  2017-07-01       Impact factor: 4.849

7.  canSAR: update to the cancer translational research and drug discovery knowledgebase.

Authors:  Elizabeth A Coker; Costas Mitsopoulos; Joesph E Tym; Angeliki Komianou; Christos Kannas; Patrizio Di Micco; Eloy Villasclaras Fernandez; Bugra Ozer; Albert A Antolin; Paul Workman; Bissan Al-Lazikani
Journal:  Nucleic Acids Res       Date:  2019-01-08       Impact factor: 16.971

8.  Benchmarking network propagation methods for disease gene identification.

Authors:  Sergio Picart-Armada; Steven J Barrett; David R Willé; Alexandre Perera-Lluna; Alex Gutteridge; Benoit H Dessailly
Journal:  PLoS Comput Biol       Date:  2019-09-03       Impact factor: 4.475

9.  The DisGeNET knowledge platform for disease genomics: 2019 update.

Authors:  Janet Piñero; Juan Manuel Ramírez-Anguita; Josep Saüch-Pitarch; Francesco Ronzano; Emilio Centeno; Ferran Sanz; Laura I Furlong
Journal:  Nucleic Acids Res       Date:  2020-01-08       Impact factor: 16.971

10.  Computational resources associating diseases with genotypes, phenotypes and exposures.

Authors:  Wenliang Zhang; Haiyue Zhang; Huan Yang; Miaoxin Li; Zhi Xie; Weizhong Li
Journal:  Brief Bioinform       Date:  2019-11-27       Impact factor: 11.622

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  57 in total

Review 1.  The PROTACtable genome.

Authors:  Melanie Schneider; Chris J Radoux; Andrew Hercules; David Ochoa; Ian Dunham; Lykourgos-Panagiotis Zalmas; Gerhard Hessler; Sven Ruf; Veerabahu Shanmugasundaram; Michael M Hann; Pam J Thomas; Markus A Queisser; Andrew B Benowitz; Kris Brown; Andrew R Leach
Journal:  Nat Rev Drug Discov       Date:  2021-07-20       Impact factor: 84.694

2.  Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation.

Authors:  Angela Serra; Michele Fratello; Antonio Federico; Ravi Ojha; Riccardo Provenzani; Ervin Tasnadi; Luca Cattelani; Giusy Del Giudice; Pia A S Kinaret; Laura A Saarimäki; Alisa Pavel; Suvi Kuivanen; Vincenzo Cerullo; Olli Vapalahti; Peter Horvath; Antonio Di Lieto; Jari Yli-Kauhaluoma; Giuseppe Balistreri; Dario Greco
Journal:  Brief Bioinform       Date:  2022-01-17       Impact factor: 11.622

3.  Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks.

Authors:  Jacob W Freimer; Oren Shaked; Sahin Naqvi; Nasa Sinnott-Armstrong; Arwa Kathiria; Christian M Garrido; Amy F Chen; Jessica T Cortez; William J Greenleaf; Jonathan K Pritchard; Alexander Marson
Journal:  Nat Genet       Date:  2022-07-11       Impact factor: 41.307

4.  Stroke genetics informs drug discovery and risk prediction across ancestries.

Authors:  Aniket Mishra; Rainer Malik; Tsuyoshi Hachiya; Tuuli Jürgenson; Shinichi Namba; Daniel C Posner; Frederick K Kamanu; Masaru Koido; Quentin Le Grand; Mingyang Shi; Yunye He; Marios K Georgakis; Ilana Caro; Kristi Krebs; Yi-Ching Liaw; Felix C Vaura; Kuang Lin; Bendik Slagsvold Winsvold; Vinodh Srinivasasainagendra; Livia Parodi; Hee-Joon Bae; Ganesh Chauhan; Michael R Chong; Liisa Tomppo; Rufus Akinyemi; Gennady V Roshchupkin; Naomi Habib; Yon Ho Jee; Jesper Qvist Thomassen; Vida Abedi; Jara Cárcel-Márquez; Marianne Nygaard; Hampton L Leonard; Chaojie Yang; Ekaterina Yonova-Doing; Maria J Knol; Adam J Lewis; Renae L Judy; Tetsuro Ago; Philippe Amouyel; Nicole D Armstrong; Mark K Bakker; Traci M Bartz; David A Bennett; Joshua C Bis; Constance Bordes; Sigrid Børte; Anael Cain; Paul M Ridker; Kelly Cho; Zhengming Chen; Carlos Cruchaga; John W Cole; Phil L de Jager; Rafael de Cid; Matthias Endres; Leslie E Ferreira; Mirjam I Geerlings; Natalie C Gasca; Vilmundur Gudnason; Jun Hata; Jing He; Alicia K Heath; Yuk-Lam Ho; Aki S Havulinna; Jemma C Hopewell; Hyacinth I Hyacinth; Michael Inouye; Mina A Jacob; Christina E Jeon; Christina Jern; Masahiro Kamouchi; Keith L Keene; Takanari Kitazono; Steven J Kittner; Takahiro Konuma; Amit Kumar; Paul Lacaze; Lenore J Launer; Keon-Joo Lee; Kaido Lepik; Jiang Li; Liming Li; Ani Manichaikul; Hugh S Markus; Nicholas A Marston; Thomas Meitinger; Braxton D Mitchell; Felipe A Montellano; Takayuki Morisaki; Thomas H Mosley; Mike A Nalls; Børge G Nordestgaard; Martin J O'Donnell; Yukinori Okada; N Charlotte Onland-Moret; Bruce Ovbiagele; Annette Peters; Bruce M Psaty; Stephen S Rich; Jonathan Rosand; Marc S Sabatine; Ralph L Sacco; Danish Saleheen; Else Charlotte Sandset; Veikko Salomaa; Muralidharan Sargurupremraj; Makoto Sasaki; Claudia L Satizabal; Carsten O Schmidt; Atsushi Shimizu; Nicholas L Smith; Kelly L Sloane; Yoichi Sutoh; Yan V Sun; Kozo Tanno; Steffen Tiedt; Turgut Tatlisumak; Nuria P Torres-Aguila; Hemant K Tiwari; David-Alexandre Trégouët; Stella Trompet; Anil Man Tuladhar; Anne Tybjærg-Hansen; Marion van Vugt; Riina Vibo; Shefali S Verma; Kerri L Wiggins; Patrik Wennberg; Daniel Woo; Peter W F Wilson; Huichun Xu; Qiong Yang; Kyungheon Yoon; Iona Y Millwood; Christian Gieger; Toshiharu Ninomiya; Hans J Grabe; J Wouter Jukema; Ina L Rissanen; Daniel Strbian; Young Jin Kim; Pei-Hsin Chen; Ernst Mayerhofer; Joanna M M Howson; Marguerite R Irvin; Hieab Adams; Sylvia Wassertheil-Smoller; Kaare Christensen; Mohammad A Ikram; Tatjana Rundek; Bradford B Worrall; G Mark Lathrop; Moeen Riaz; Eleanor M Simonsick; Janika Kõrv; Paulo H C França; Ramin Zand; Kameshwar Prasad; Ruth Frikke-Schmidt; Frank-Erik de Leeuw; Thomas Liman; Karl Georg Haeusler; Ynte M Ruigrok; Peter Ulrich Heuschmann; W T Longstreth; Keum Ji Jung; Lisa Bastarache; Guillaume Paré; Scott M Damrauer; Daniel I Chasman; Jerome I Rotter; Christopher D Anderson; John-Anker Zwart; Teemu J Niiranen; Myriam Fornage; Yung-Po Liaw; Sudha Seshadri; Israel Fernández-Cadenas; Robin G Walters; Christian T Ruff; Mayowa O Owolabi; Jennifer E Huffman; Lili Milani; Yoichiro Kamatani; Martin Dichgans; Stephanie Debette
Journal:  Nature       Date:  2022-09-30       Impact factor: 69.504

Review 5.  Predictive validity in drug discovery: what it is, why it matters and how to improve it.

Authors:  Jack W Scannell; James Bosley; John A Hickman; Gerard R Dawson; Hubert Truebel; Guilherme S Ferreira; Duncan Richards; J Mark Treherne
Journal:  Nat Rev Drug Discov       Date:  2022-10-04       Impact factor: 112.288

6.  Text Mining Protocol to Retrieve Significant Drug-Gene Interactions from PubMed Abstracts.

Authors:  Oviya Ramalakshmi Iyyappan; Sharanya Manoharan; Sadhanha Anand; Dheepa Anand; Manonmani Alvin Jose; Raja Ravi Shanker
Journal:  Methods Mol Biol       Date:  2022

7.  Investigation of the mechanism of Shen Qi Wan prescription in the treatment of T2DM via network pharmacology and molecular docking.

Authors:  Piaopiao Zhao; Xiaoxiao Zhang; Yuning Gong; Weihua Li; Zengrui Wu; Yun Tang; Guixia Liu
Journal:  In Silico Pharmacol       Date:  2022-06-04

Review 8.  Trends in kinase drug discovery: targets, indications and inhibitor design.

Authors:  Misty M Attwood; Doriano Fabbro; Aleksandr V Sokolov; Stefan Knapp; Helgi B Schiöth
Journal:  Nat Rev Drug Discov       Date:  2021-08-05       Impact factor: 84.694

9.  Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells.

Authors:  Alaa Sayed Abou-Elhamd; Gauthaman Kalamegam; Farid Ahmed; Mourad Assidi; Abdulmajeed Fahad Alrefaei; Peter Natesan Pushparaj; Muhammad Abu-Elmagd
Journal:  Front Pharmacol       Date:  2021-05-10       Impact factor: 5.810

10.  Transcriptional-regulatory convergence across functional MDD risk variants identified by massively parallel reporter assays.

Authors:  Bernard Mulvey; Joseph D Dougherty
Journal:  Transl Psychiatry       Date:  2021-07-22       Impact factor: 6.222

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