A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

大部分生物医学研究和治疗方法的开发都集中在人类基因组的一小部分。为了绘制人类基因组编码蛋白质的知识差距并促进对目前尚未充分研究但可能可药物化的蛋白质的探索，美国国立卫生研究院于 2014 年发起了“阐明可药物基因组 (IDG)”计划。在本文中，我们讨论 IDG 知识管理中心如何系统地收集和处理大量基因组、蛋白质组、化学和疾病相关资源数据，从而制定跟踪目标发展水平的循证标准（人类蛋白质的 TDL），这表明人类蛋白质组中大约三分之一的蛋白质存在严重的知识缺陷。然后，我们重点关注 TDL 类别以及关键药物靶标类别，包括 G 蛋白偶联受体、蛋白激酶和离子通道，这些都说明了生物医学研究和治疗开发中尚未探索的机会的本质。