Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

基于生物网络分析技术浅析“肺与大肠相表里”理论

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

目的利用现代生物网络研究肺炎与结肠炎的共性病机,基于此探讨“肺与大肠相表里”理论。方法在GeneCards数据库分别查询肺炎、结肠炎的相关靶点,根据相关性得分筛选得出两种疾病的主要靶点并进行交集,得到二者共有靶点;利用Metascape数据库对肺炎、结肠炎主要靶点及共有靶点进行分析,同时通过DAVID数据库对共有靶点进行富集分析;使用Cytoscape 3.7.2软件构建网络图。结果预测出肺炎和结肠炎的发生存在TNF、IL-10、IL-6、IL-2、IL-4、TLR4、TLR2、CXCL8、IL-17A、IFNG等54个共同靶点,并主要富集于Cytokine-cytokine receptor interaction、T cell receptor signaling pathway、Toll-like receptor signaling pathway和Jak-STAT signaling pathway等通路上。Metascape数据库的模块化分析结果显示:有11个模块与肺炎发生有关、6个模块与结肠炎发生有关、2个共有模块与肺炎和结肠炎发生同时相关。结论肺炎与结肠炎之间存在共同的致病靶点和作用机制,并最终通过炎症反应、免疫应答等相互作用,可以尝试用现代分子机制阐释“肺与大肠相表里”理论。