Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery

被引：10

作者：

Buniello, Annalisa ^{[1
,2
]}

Suveges, Daniel ^{[1
,2
]}

Cruz-Castillo, Carlos ^{[1
,2
]}

Llinares, Manuel Bernal ^{[1
,2
]}

Cornu, Helena ^{[1
,2
]}

Lopez, Irene ^{[1
,2
]}

Tsukanov, Kirill ^{[1
,2
]}

Roldan-Romero, Juan Maria ^{[1
,2
]}

Mehta, Chintan ^{[1
,2
]}

Fumis, Luca ^{[1
,2
]}

Mcneill, Graham ^{[1
,2
]}

Hayhurst, James D. ^{[1
,2
]}

Osorio, Ricardo Esteban Martinez ^{[1
,2
]}

Barkhordari, Ehsan ^{[1
,2
]}

Ferrer, Javier ^{[1
,2
]}

Carmona, Miguel ^{[3
]}

Uniyal, Prashant ^{[1
,2
]}

Falaguera, Maria J. ^{[1
,2
]}

Rusina, Polina ^{[1
,2
]}

Smit, Ines ^{[1
,2
]}

Schwartzentruber, Jeremy ^{[1
,4
]}

Alegbe, Tobi ^{[1
,2
]}

Ho, Vivien W. ^{[1
,2
]}

Considine, Daniel ^{[1
,4
]}

Ge, Xiangyu ^{[1
,4
]}

Szyszkowski, Szymon ^{[1
,4
]}

Tsepilov, Yakov ^{[1
,4
]}

Ghoussaini, Maya ^{[1
,4
]}

Dunham, Ian ^{[1
,2
,4
]}

Hulcoop, David G. ^{[1
,2
,4
]}

Mcdonagh, Ellen M. ^{[1
,2
,4
]}

Ochoa, David ^{[1
,2
,4
]}

机构：

[1] Open Targets, Wellcome Genome Campus, Hinxton CB10 1SD, Cambs, England

[2] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Genome Campus, Hinxton CB10 1SD, Cambs, England

[3] AstraZeneca UK Ltd, Cambridge, England

[4] Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton CB10 1SA, Cambs, England

来源：

NUCLEIC ACIDS RESEARCH | 2024年 / 53卷 / D1期

基金：

英国惠康基金;

关键词：

INSIGHTS; CHEMBL;

D O I：

10.1093/nar/gkae1128

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Open Targets Platform (https://platform.opentargets.org) is a unique, open-source, publicly-available knowledge base providing data and tooling for systematic drug target identification, annotation, and prioritisation. Since our last report, we have expanded the scope of the Platform through a number of significant enhancements and data updates, with the aim to enable our users to formulate more flexible and impactful therapeutic hypotheses. In this context, we have completely revamped our target-disease associations page with more interactive facets and built-in functionalities to empower users with additional control over their experience using the Platform, and added a new Target Prioritisation view. This enables users to prioritise targets based upon clinical precedence, tractability, doability and safety attributes. We have also implemented a direction of effect assessment for eight sources of target-disease association evidence, showing the effect of genetic variation on the function of a target is associated with risk or protection for a trait to inform on potential mechanisms of modulation suitable for disease treatment. These enhancements and the introduction of new back and front-end technologies to support them have increased the impact and usability of our resource within the drug discovery community.

引用

页码：D1467 / D1475

页数：9

共 61 条

[1] The GTEx Consortium atlas of genetic regulatory effects across human tissues [J].

Aguet, Francois ;

Barbeira, Alvaro N. ;

Bonazzola, Rodrigo ;

Brown, Andrew ;

Castel, Stephane E. ;

Jo, Brian ;

Kasela, Silva ;

Kim-Hellmuth, Sarah ;

Liang, Yanyu ;

Parsana, Princy ;

Flynn, Elise ;

Fresard, Laure ;

Gamazon, Eric R. ;

Hamel, Andrew R. ;

He, Yuan ;

Hormozdiari, Farhad ;

Mohammadi, Pejman ;

Munoz-Aguirre, Manuel ;

Ardlie, Kristin G. ;

Battle, Alexis ;

Bonazzola, Rodrigo ;

Brown, Christopher D. ;

Cox, Nancy ;

Dermitzakis, Emmanouil T. ;

Engelhardt, Barbara E. ;

Garrido-Martin, Diego ;

Gay, Nicole R. ;

Getz, Gad ;

Guigo, Roderic ;

Hamel, Andrew R. ;

Handsaker, Robert E. ;

He, Yuan ;

Hoffman, Paul J. ;

Hormozdiari, Farhad ;

Im, Hae Kyung ;

Jo, Brian ;

Kasela, Silva ;

Kashin, Seva ;

Kim-Hellmuth, Sarah ;

Kwong, Alan ;

Lappalainen, Tuuli ;

Li, Xiao ;

Liang, Yanyu ;

MacArthur, Daniel G. ;

Mohammadi, Pejman ;

Montgomery, Stephen B. ;

Munoz-Aguirre, Manuel ;

Rouhana, John M. ;

Hormozdiari, Farhad ;

Im, Hae Kyung .

SCIENCE, 2020, 369 (6509) :1318-1330

[2] Mouse Genome Informatics: an integrated knowledgebase system for the laboratory mouse [J].

Baldarelli, Richard M. ;

Smith, Cynthia L. ;

Ringwald, Martin ;

Richardson, Joel E. ;

Bult, Carol J. .

GENETICS, 2024, 227 (01)

[3] UniProt: the Universal Protein Knowledgebase in 2023 [J].

Bateman, Alex ;

Martin, Maria-Jesus ;

Orchard, Sandra ;

Magrane, Michele ;

Ahmad, Shadab ;

Alpi, Emanuele ;

Bowler-Barnett, Emily H. ;

Britto, Ramona ;

Cukura, Austra ;

Denny, Paul ;

Dogan, Tunca ;

Ebenezer, ThankGod ;

Fan, Jun ;

Garmiri, Penelope ;

Gonzales, Leonardo Jose da Costa ;

Hatton-Ellis, Emma ;

Hussein, Abdulrahman ;

Ignatchenko, Alexandr ;

Insana, Giuseppe ;

Ishtiaq, Rizwan ;

Joshi, Vishal ;

Jyothi, Dushyanth ;

Kandasaamy, Swaathi ;

Lock, Antonia ;

Luciani, Aurelien ;

Lugaric, Marija ;

Luo, Jie ;

Lussi, Yvonne ;

MacDougall, Alistair ;

Madeira, Fabio ;

Mahmoudy, Mahdi ;

Mishra, Alok ;

Moulang, Katie ;

Nightingale, Andrew ;

Pundir, Sangya ;

Qi, Guoying ;

Raj, Shriya ;

Raposo, Pedro ;

Rice, Daniel L. ;

Saidi, Rabie ;

Santos, Rafael ;

Speretta, Elena ;

Stephenson, James ;

Totoo, Prabhat ;

Turner, Edward ;

Tyagi, Nidhi ;

Vasudev, Preethi ;

Warner, Kate ;

Watkins, Xavier ;

Zellner, Hermann .

NUCLEIC ACIDS RESEARCH, 2023, 51 (D1) :D523-D531

[4] Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura [J].

Bjornsdottir, Gyda ;

Chalmer, Mona A. ;

Stefansdottir, Lilja ;

Skuladottir, Astros Th. ;

Einarsson, Gudmundur ;

Andresdottir, Margret ;

Beyter, Doruk ;

Ferkingstad, Egil ;

Gretarsdottir, Solveig ;

Halldorsson, Bjarni V. ;

Halldorsson, Gisli H. ;

Helgadottir, Anna ;

Helgason, Hannes ;

Eldjarn, Grimur Hjorleifsson ;

Jonasdottir, Adalbjorg ;

Jonasdottir, Aslaug ;

Jonsdottir, Ingileif ;

Knowlton, Kirk U. ;

Nadauld, Lincoln D. ;

Lund, Sigrun H. ;

Magnusson, Olafur Th. ;

Melsted, Pall ;

Moore, Kristjan H. S. ;

Oddsson, Asmundur ;

Olason, Pall I. ;

Sigurdsson, Asgeir ;

Stefansson, Olafur A. ;

Saemundsdottir, Jona ;

Sveinbjornsson, Gardar ;

Tragante, Vinicius ;

Unnsteinsdottir, Unnur ;

Walters, G. Bragi ;

Zink, Florian ;

Rodevand, Linn ;

Andreassen, Ole A. ;

Igland, Jannicke ;

Lie, Rolv T. ;

Haavik, Jan ;

Banasik, Karina ;

Brunak, Soren ;

Didriksen, Maria ;

Bruun, Mie T. ;

Erikstrup, Christian ;

Kogelman, Lisette J. A. ;

Nielsen, Kaspar R. ;

Sorensen, Erik ;

Pedersen, Ole B. ;

Ullum, Henrik ;

Masson, Gisli ;

Thorsteinsdottir, Unnur .

NATURE GENETICS, 2023, 55 (11) :1843-+

[5] The state of the art in secondary pharmacology and its impact on the safety of new medicines [J].

Brennan, Richard J. ;

Jenkinson, Stephen ;

Brown, Andrew ;

Delaunois, Annie ;

Dumotier, Berengere ;

Pannirselvam, Malar ;

Rao, Mohan ;

Ribeiro, Lyn Rosenbrier ;

Schmidt, Friedemann ;

Sibony, Alicia ;

Timsit, Yoav ;

Sales, Vicencia Toledo ;

Armstrong, Duncan ;

Lagrutta, Armando ;

Mittlestadt, Scott W. ;

Naven, Russell ;

Peri, Ravikumar ;

Roberts, Sonia ;

Vergis, James M. ;

Valentin, Jean-Pierre .

NATURE REVIEWS DRUG DISCOVERY, 2024, 23 (07) :525-545

[6] Open Targets Platform: new developments and updates two years on [J].

Carvalho-Silva, Denise ;

Pierleoni, Andrea ;

Pignatelli, Miguel ;

Ong, ChuangKee ;

Fumis, Luca ;

Karamanis, Nikiforos ;

Carmona, Miguel ;

Faulconbridge, Adam ;

Hercules, Andrew ;

McAuley, Elaine ;

Miranda, Alfredo ;

Peat, Gareth ;

Spitzer, Michaela ;

Barrett, Jeffrey ;

Hulcoop, David G. ;

Papa, Eliseo ;

Koscielny, Gautier ;

Dunham, Ian .

NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D1056-D1065

[7] Accurate proteome-wide missense variant effect prediction with AlphaMissense [J].

Cheng, Jun ;

Novati, Guido ;

Pan, Joshua ;

Bycroft, Clare ;

Zemgulyte, Akvile ;

Applebaum, Taylor ;

Pritzel, Alexander ;

Wong, Lai Hong ;

Zielinski, Michal ;

Sargeant, Tobias ;

Schneider, Rosalia G. ;

Senior, Andrew W. ;

Jumper, John ;

Hassabis, Demis ;

Kohli, Pushmeet ;

Avsec, Ziga .

SCIENCE, 2023, 381 (6664) :1303-+

[8] TargetDB: A target information aggregation tool and tractability predictor [J].

De Cesco, Stephane ;

Davis, John B. ;

Brennan, Paul E. .

PLOS ONE, 2020, 15 (09)

[9] canSAR: update to the cancer translational research and drug discovery knowledgebase [J].

di Micco, Patrizio ;

Antolin, Albert A. ;

Mitsopoulos, Costas ;

Villasclaras-Fernandez, Eloy ;

Sanfelice, Domenico ;

Dolciami, Daniela ;

Ramagiri, Pradeep ;

Mica, Ioan L. ;

Tym, Joseph E. ;

Gingrich, Philip W. ;

Hu, Huabin ;

Workman, Paul ;

Al-Lazikani, Bissan .

NUCLEIC ACIDS RESEARCH, 2023, 51 (D1) :D1212-D1219

[10] Trends in clinical success rates and therapeutic focus [J].

Dowden, Helen ;

Munro, Jamie .

NATURE REVIEWS DRUG DISCOVERY, 2019, 18 (07) :494-495

← 1 2 3 4 5 6 7 →