Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA; UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Drug Discov Today. 2022 Jun;27(6):1671-1678. doi: 10.1016/j.drudis.2022.02.008. Epub 2022 Feb 16.
Here, we propose a broad concept of 'Clinical Outcome Pathways' (COPs), which are defined as a series of key molecular and cellular events that underlie therapeutic effects of drug molecules. We formalize COPs as a chain of the following events: molecular initiating event (MIE) → intermediate event(s) → clinical outcome. We illustrate the concept with COP examples both for primary and alternative (i.e., drug repurposing) therapeutic applications. We also describe the elucidation of COPs for several drugs of interest using the publicly accessible Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) biomedical knowledge graph-mining tool. We propose that broader use of COP uncovered with the help of biomedical knowledge graph mining will likely accelerate drug discovery and repurposing efforts.
在这里，我们提出了“临床结果途径”（COPs）的广义概念，它被定义为一系列潜在药物分子治疗效果的关键分子和细胞事件。我们将 COPs 形式化为以下事件的链：分子起始事件（MIE）→中间事件→临床结果。我们通过原发性和替代性（即药物再利用）治疗应用的 COP 示例来说明该概念。我们还描述了使用可公开访问的 Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) 生物医学知识图挖掘工具阐明几种有价值药物的 COPs 的过程。我们提出，借助生物医学知识图挖掘发现的更广泛的 COP 将可能加速药物发现和再利用的努力。
