Development of a Human Genetics-guided Priority Score for 19,365 Genes and 399 Drug Indications

Overview

Journal Nat Genet

Specialty Genetics

Date 2024 Jan 3

PMID 38172303

Authors

Aine Duffy

Ben Omega Petrazzini

David Stein

Joshua K Park

Iain S Forrest

Kyle Gibson

Ha My Vy

Robert Chen

Carla Marquez-Luna

Matthew Mort

Marie Verbanck

Avner Schlessinger

Yuval Itan

David N Cooper

Ghislain Rocheleau

Daniel M Jordan

Ron Do

Affiliations

Soon will be listed here.

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.

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