Duffy, Áine, Petrazzini, Ben Omega, Stein, David, Park, Joshua K., Forrest, Iain S., Gibson, Kyle, Vy, Ha My, Chen, Robert, Márquez-Luna, Carla, Mort, Matthew, Verbanck, Marie, Schlessinger, Avner, Itan, Yuval, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484, Rocheleau, Ghislain, Jordan, Daniel M. and Do, Ron 2024. Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications. Nature Genetics 56 (1) , pp. 51-59. 10.1038/s41588-023-01609-2 |
Abstract
Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. In addition, we observed that targets in the top 0.28% of the score were 1.7-, 3.7- and 8.8-fold more likely to advance from phase I to phases II, III and IV, respectively. Complementary to the GPS, we incorporated the direction of genetic effect and drug mechanism into a directional version of the score called the GPS with direction of effect. We applied our method to 19,365 protein-coding genes and 399 drug indications and made all results available through a web portal.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Medicine |
Publisher: | Nature Research |
ISSN: | 1061-4036 |
Date of First Compliant Deposit: | 8 April 2024 |
Date of Acceptance: | 13 November 2023 |
Last Modified: | 12 Apr 2024 14:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/167800 |
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