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.

中文翻译：

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开放目标平台：支持系统的药物目标识别和优先级排序

摘要

开放目标平台（https://www.targetvalidation.org/）为用户提供可查询的知识库和用户界面，以帮助根据基础证据对药物发现进行系统的目标识别和优先级排序。它是公开可用的，基础代码是开源的。自两年前的最新更新以来，我们已经发布了10个版本，以维护和不断改进来自20个不同数据源的目标疾病关系的证据。此外，我们还整合了来自关键数据集的新证据，包括从300个癌症模型的全基因组CRISPR敲除筛选中确定的优先目标（项目得分），以及来自开放目标遗传学门户网站的GWAS / UK BioBank统计遗传分析证据。我们已经改进了证据评分框架，以改善目标识别。为了帮助确定目标的优先级并告知调整给定目标的潜在影响，我们增加了对上市后药品不良反应的评估，并提供了有关目标可处理性和安全性的新精选信息。我们还开发了用户界面和后端技术，以提高性能和可用性。在本文中，我们描述了平台的最新增强功能，以解决开发有效且安全的药物既困难又昂贵的根本挑战。