Text Mining-Based Drug Discovery for Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.
Text Mining-Based Drug Discovery for Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.
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基于文本挖掘的结缔组织病药物发现 - 相关肺动脉高压
DOI：
10.3389/fphar.2022.743210
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发表时间：
2022
影响因子：
5.6
通讯作者：
Wang XJ
中科院分区：
文献类型：
--
作者：
Tan JS;Hu S;Guo TT;Hua L;Wang XJ
背景：目前治疗结缔组织病相关性肺动脉高压(CTD-PAH)的药物并不是对所有患者都有良好的疗效，需要寻找新的药物。方法：通过文本挖掘获得CTD和PAH相关基因集，并通过David软件对两个基因集的交集进行功能丰富分析。用STRING确定重叠基因和重要基因模块的蛋白质-蛋白质相互作用网络。进一步利用药物基因相互作用数据库对丰富的候选基因进行分析，筛选出对CTD-PAH有潜在治疗作用的药物。结果：基于文本挖掘分析，共鉴定出179个与CTD和PAH相关的基因。通过对这些基因的富集化分析，获得了20个基因，分别代表6条途径。为了进一步缩小潜在的现有药物的范围，我们选择了查询分数为≥5，相互作用分数为≥1的靶向药物。最终，针对这6个基因的13个药物被选为候选药物，分为4种药物-基因相互作用类型，其中12个药物具有美国食品和药物管理局批准的初始药物适应症。这份清单上的药物的潜在基因靶点是IL-6(一种药物)和IL-1β(两种药物)、MMP9(一种药物)、VEGFA(三种药物)、TGFB1(一种药物)和EGFR(五种药物)。这些药物可能用于治疗CTD-PAH。结论：我们确定了13种针对6个基因的药物，它们可能对CTD-PAH有潜在的治疗作用。
Background: The current medical treatments for connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) do not show favorable efficiency for all patients, and identification of novel drugs is desired. Methods: Text mining was performed to obtain CTD- and PAH-related gene sets, and the intersection of the two gene sets was analyzed for functional enrichment through DAVID. The protein–protein interaction network of the overlapping genes and the significant gene modules were determined using STRING. The enriched candidate genes were further analyzed by Drug Gene Interaction database to identify drugs with potential therapeutic effects on CTD-PAH. Results: Based on text mining analysis, 179 genes related to CTD and PAH were identified. Through enrichment analysis of the genes, 20 genes representing six pathways were obtained. To further narrow the scope of potential existing drugs, we selected targeted drugs with a Query Score ≥5 and Interaction Score ≥1. Finally, 13 drugs targeting the six genes were selected as candidate drugs, which were divided into four drug–gene interaction types, and 12 of them had initial drug indications approved by the FDA. The potential gene targets of the drugs on this list are IL-6 (one drug) and IL-1β (two drugs), MMP9 (one drug), VEGFA (three drugs), TGFB1 (one drug), and EGFR (five drugs). These drugs might be used to treat CTD-PAH. Conclusion: We identified 13 drugs targeting six genes that may have potential therapeutic effects on CTD-PAH.
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