Ratnam Joseline, Zdrazil Barbara, Digles Daniela, Cuadrado-Rodriguez Emiliano, Neefs Jean-Marc, Tipney Hannah, Siebes Ronald, Waagmeester Andra, Bradley Glyn, Chau Chau Han, Richter Lars, Brea Jose, Evelo Chris T, Jacoby Edgar, Senger Stefan, Loza Maria Isabel, Ecker Gerhard F, Chichester Christine
Universidade de Santiago de Compostela, Grupo BioFarma-USEF, Departamento de Farmacología, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
PLoS One. 2014 Dec 18;9(12):e115460. doi: 10.1371/journal.pone.0115460. eCollection 2014.
Integration of open access, curated, high-quality information from multiple disciplines in the Life and Biomedical Sciences provides a holistic understanding of the domain. Additionally, the effective linking of diverse data sources can unearth hidden relationships and guide potential research strategies. However, given the lack of consistency between descriptors and identifiers used in different resources and the absence of a simple mechanism to link them, gathering and combining relevant, comprehensive information from diverse databases remains a challenge. The Open Pharmacological Concepts Triple Store (Open PHACTS) is an Innovative Medicines Initiative project that uses semantic web technology approaches to enable scientists to easily access and process data from multiple sources to solve real-world drug discovery problems. The project draws together sources of publicly-available pharmacological, physicochemical and biomolecular data, represents it in a stable infrastructure and provides well-defined information exploration and retrieval methods. Here, we highlight the utility of this platform in conjunction with workflow tools to solve pharmacological research questions that require interoperability between target, compound, and pathway data. Use cases presented herein cover 1) the comprehensive identification of chemical matter for a dopamine receptor drug discovery program 2) the identification of compounds active against all targets in the Epidermal growth factor receptor (ErbB) signaling pathway that have a relevance to disease and 3) the evaluation of established targets in the Vitamin D metabolism pathway to aid novel Vitamin D analogue design. The example workflows presented illustrate how the Open PHACTS Discovery Platform can be used to exploit existing knowledge and generate new hypotheses in the process of drug discovery.
整合生命科学和生物医学多个学科的开放获取、经过整理的高质量信息，有助于全面了解该领域。此外，有效链接不同数据源可以挖掘隐藏关系并指导潜在的研究策略。然而，由于不同资源中使用的描述符和标识符缺乏一致性，且缺乏简单的链接机制，从不同数据库收集和整合相关的全面信息仍然是一项挑战。开放药理学概念三元组存储库（Open PHACTS）是一项创新药物倡议项目，它使用语义网技术方法，使科学家能够轻松访问和处理来自多个来源的数据，以解决现实世界中的药物发现问题。该项目汇集了公开可用的药理学、物理化学和生物分子数据来源，在稳定的基础设施中对其进行表示，并提供定义明确的信息探索和检索方法。在这里，我们强调该平台与工作流程工具结合使用的效用，以解决需要靶标、化合物和通路数据之间互操作性的药理学研究问题。本文介绍的用例包括：1）多巴胺受体药物发现项目中化学物质的全面鉴定；2）鉴定对表皮生长因子受体（ErbB）信号通路中所有与疾病相关的靶标具有活性的化合物；3）评估维生素D代谢途径中已确定的靶标，以辅助新型维生素D类似物的设计。所展示的示例工作流程说明了Open PHACTS发现平台如何用于在药物发现过程中利用现有知识并生成新的假设。
