Sun Shixue, Tian Yitao, Zhu Qian
Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Rockville, USA.
Proceedings (IEEE Int Conf Bioinformatics Biomed). 2023 Dec;2023:2748-2750. doi: 10.1109/bibm58861.2023.10385957. Epub 2024 Jan 18.
The purpose of drug repurposing is to identify alternative uses of FDA approved drugs, which significantly accelerates the drug development process. Meanwhile, clinical data illustrate the patterns and clinical outcomes of drug use, so they have been increasingly applied to support drug development, particularly for drug repurposing. The NIH Biomedical Translational Research Information System (BTRIS) is a resource which compiles deidentified patient data from clinical research done across NIH Institutes and Centers. In this study, we analyzed clinical data available from BTRIS to identify drug repurposing candidates, i.e., identifying drugs that were correlated with an increased survival rate for glioblastoma (GBM) patients. Specifically, we extracted all the administered drugs on GBM patients and fitted them to elastic-net penalized Cox proportional hazards (CPH) models, a regression model for investigating the association between the survival rate of patients and covariates (administered drugs in this study). We were able to identify several potential drug candidates for GBM to be further evaluated with other data types and by performing biological experiments.
药物重新利用的目的是确定美国食品药品监督管理局（FDA）批准药物的其他用途，这显著加速了药物研发过程。同时，临床数据阐明了药物使用的模式和临床结果，因此它们越来越多地被用于支持药物研发，特别是在药物重新利用方面。美国国立卫生研究院（NIH）的生物医学转化研究信息系统（BTRIS）是一个汇集了来自NIH各研究所和中心开展的临床研究中已去除身份标识的患者数据的资源库。在本研究中，我们分析了BTRIS中可用的临床数据，以识别药物重新利用的候选药物，即识别与胶质母细胞瘤（GBM）患者生存率提高相关的药物。具体而言，我们提取了所有给予GBM患者的药物，并将其拟合到弹性网惩罚Cox比例风险（CPH）模型中，这是一种用于研究患者生存率与协变量（本研究中的给药药物）之间关联的回归模型。我们能够识别出几种GBM潜在的候选药物，有待通过其他数据类型并进行生物学实验作进一步评估。
