European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
Nucleic Acids Res. 2021 Jan 8;49(D1):D1302-D1310. doi: 10.1093/nar/gkaa1027.
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.
Open Targets 平台(https://www.targetvalidation.org/)为用户提供了一个可查询的知识库和用户界面,以帮助在药物发现中基于潜在证据进行系统的目标识别和优先级排序。它是公开的,底层代码是开源的。自我们两年前的最后一次更新以来,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 种癌症模型中的全基因组 CRISPR 敲除筛选中确定的优先靶点(Project Score),以及来自 Open Targets Genetics Portal 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,以提高目标识别能力。为了帮助目标的优先级排序,并提供关于调节特定目标的潜在影响的信息,我们还增加了对上市后药物不良反应的评估,以及关于目标可操作性和安全性的新的精心策划的信息。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,以解决开发有效和安全药物困难且昂贵的根本挑战。