基于互信息的药物重新定位用于治疗阿尔茨海默病患者。
Drug repositioning based on mutual information for the treatment of Alzheimer's disease patients.
作者信息
Cava Claudia, Castiglioni Isabella
机构信息
Department of Science, Technology and Society, University School for Advanced Studies IUSS Pavia, Palazzo del Broletto, Piazza Della Vittoria 15, 27100, Pavia, Italy.
Department of Physics ''Giuseppe Occhialini", University of Milan-Bicocca, Piazza Dell'Ateneo Nuovo, 20126, Milan, Italy.
出版信息
Med Biol Eng Comput. 2025 Feb 17. doi: 10.1007/s11517-025-03325-x.
Computational drug repositioning approaches should be investigated for the identification of new treatments for Alzheimer's patients as a huge amount of omics data has been produced during pre-clinical and clinical studies. Here, we investigated a gene network in Alzheimer's patients to detect a proper therapeutic target. We screened the targets of different drugs (34,006 compounds) using data available in the Connectivity Map database. Then, we analyzed transcriptome profiles of Alzheimer's patients to discover a network of gene-drugs based on mutual information, representing an index of dependence among genes. This study identified a network consisting of 25 genes and compounds and interconnected biological processes using computational approaches. The results also highlight the diagnostic role of the 25 genes since we obtained good classification performances using a neural network model. We also suggest 12 repurposable drugs (like KU-60019, AM-630, CP55940, enflurane, ginkgolide B, linopirdine, apremilast, ibudilast, pentoxifylline, roflumilast, acitretin, and tamibarotene) interacting with 6 genes (ATM, CNR1, GLRB, KCNQ2, PDE4B, and RARA), that we linked to retrograde endocannabinoid signaling, synaptic vesicle cycle, morphine addiction, and homologous recombination.
由于在临床前和临床研究期间已经产生了大量的组学数据,因此应该研究计算药物重新定位方法,以确定阿尔茨海默病患者的新治疗方法。在这里,我们研究了阿尔茨海默病患者的基因网络,以检测合适的治疗靶点。我们使用连通性图谱数据库中可用的数据筛选了不同药物(34,006种化合物)的靶点。然后,我们分析了阿尔茨海默病患者的转录组谱,以基于互信息发现基因-药物网络,互信息代表基因之间的依赖指数。本研究使用计算方法确定了一个由25个基因和化合物以及相互关联的生物学过程组成的网络。结果还突出了这25个基因的诊断作用,因为我们使用神经网络模型获得了良好的分类性能。我们还提出了12种可重新利用的药物(如KU-60019、AM-630、CP55940、恩氟烷、银杏内酯B、利诺吡啶、阿普司特、异丁司特、己酮可可碱、罗氟司特、阿维A和他米巴罗汀),它们与6个基因(ATM、CNR1、GLRB、KCNQ2、PDE4B和RARA)相互作用,我们将这些基因与逆行内源性大麻素信号传导、突触小泡循环、吗啡成瘾和同源重组联系起来。