美国纽约西奈山伊坎医学院Ron Do团队近期取得重要工作进展，他们研究开发了人类遗传学指导的19,365个基因和399个药物适应症的优先评分方法。相关研究成果2024年1月3日在线发表于《自然—遗传学》杂志上。

据介绍，研究表明，具有人类基因支持的药物靶点更有可能在临床试验中取得成功。因此，整合遗传证据以优先考虑药物靶基因的工具有利于药物发现。

研究人员通过整合来自Open Targets和SIDER数据库的8个遗传特征与药物适应症建立了遗传优先评分(GPS)。GPS排名前0.83%、0.28%和0.19%的人，其具有适应症的效果分别提高了5.3倍、9.9倍和11.0倍。

此外，研究人员观察到，GPS排名前0.28%的人从第I期进入II期、III期和IV期的可能性分别高出1.7倍、3.7倍和8.8倍。作为GPS的补充，研究人员将遗传效应的方向和药物机制纳入了一个定向版本的评分，称为具有效应方向的GPS。

总之，研究人员将这一方法应用于19365个蛋白质编码基因和399个药物适应症，并通过门户网站提供所有结果。

附：英文原文

Title: Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications

Author: Duffy, ine, Petrazzini, Ben Omega, Stein, David, Park, Joshua K., Forrest, Iain S., Gibson, Kyle, Vy, Ha My, Chen, Robert, Mrquez-Luna, Carla, Mort, Matthew, Verbanck, Marie, Schlessinger, Avner, Itan, Yuval, Cooper, David N., Rocheleau, Ghislain, Jordan, Daniel M., Do, Ron

Issue&Volume: 2024-01-03

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.

DOI: 10.1038/s41588-023-01609-2

Source: https://www.nature.com/articles/s41588-023-01609-2