Zaman Shadia, Sarntivijai Sirarat, Abernethy Darrell R
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
Gene Regul Syst Bio. 2017 Mar 15;11:1177625017696075. doi: 10.1177/1177625017696075. eCollection 2017.
Drug-induced toxicity is a major public health concern that leads to patient morbidity and mortality. To address this problem, the Food and Drug Administration is working on the PredicTox initiative, a pilot research program on tyrosine kinase inhibitors, to build mechanistic and predictive models for drug-induced toxicity. This program involves integrating data acquired during preclinical studies and clinical trials within pharmaceutical company development programs that they have agreed to put in the public domain and in publicly available biological, pharmacological, and chemical databases. The integration process is accommodated by biomedical ontologies, a set of standardized vocabularies that define terms and logical relationships between them in each vocabulary. We describe a few programs that have used ontologies to address biomedical questions. The PredicTox effort is leveraging the experience gathered from these early initiatives to develop an infrastructure that allows evaluation of the hypothesis that having a mechanistic understanding underlying adverse drug reactions will improve the capacity to understand drug-induced clinical adverse drug reactions.
药物诱导的毒性是一个重大的公共卫生问题，会导致患者发病和死亡。为解决这一问题，美国食品药品监督管理局正在开展“预测毒性”计划，这是一项关于酪氨酸激酶抑制剂的试点研究项目，旨在建立药物诱导毒性的机制模型和预测模型。该项目包括整合在临床前研究和临床试验期间获取的数据，这些数据来自制药公司开发项目中已同意公开的部分，以及公开可用的生物学、药理学和化学数据库。生物医学本体为整合过程提供了支持，生物医学本体是一组标准化词汇表，在每个词汇表中定义术语及其之间的逻辑关系。我们介绍一些利用本体来解决生物医学问题的项目。“预测毒性”计划正在利用从这些早期项目中积累的经验，来开发一个基础设施，以便评估这样一个假设，即对药物不良反应有机制上的理解将提高理解药物诱导的临床不良反应的能力。
