基于生物信息学探究系统性硬化-系统性红斑狼疮重叠综合征的病理机制

Pathological mechanism of systemic sclerosis-systemic lupus erythematosus overlap syndrome based on bioinformatics

目的:通过生物信息学方法寻找系统性硬化(SSc)和系统性红斑狼疮(SLE)的分子联系,探究SSc-SLE重叠综合征的病理机制。方法:从DisGeNET数据库下载两种疾病相关基因,选取存在互作的基因构建蛋白互作网络,提取该网络中最大的连接成分作为子网络命名为SSN,分析拓扑特征,采用MCODE插件挖掘SSN网络的关键基因功能集和功能模块,R软件ClusterProfiler包进行GO和KEGG富集分析。寻找疾病相关lncRNA构建lncRNA-基因调控网络。结果:SSN包含372个代表疾病相关基因的节点,470条代表基因间互作的边。关键基因功能集由CREB3L1、REL、MUC1、TRAF2、LCN2、IKZF3、PIN1、PFDN5、TRIM27、GEM 10个基因构成。MCODE插件发现了2个功能模块,GO分析表明M1模块富集于CXCR趋化因子受体结合、细胞因子受体结合等分子功能,M2模块则富集于CARD结构域结合、泛素-蛋白质转移酶调节活性等。建立了lncRNA-基因调控网络。结论:SSN中关键基因功能集、功能模块和lncRNA-基因调控网络丰富了对SLE和SSc分子病理学联系的认识,为进一步探索SSc-SLE重叠综合征病理机制和干预靶点提供了可靠的研究视角。

Objective:To find molecular link between systemic sclerosis(SSc)and systemic lupus erythematosus(SLE)by bioinformatics methods,and to explore pathological mechanism of SSc-SLE overlap syndrome.Methods:Disease-related genes were downloaded from DisGeNET database,interacting genes were mapped into PPI network,and maximum connecting component was extracted as a protein interaction sub-network,which was named as SSN.Topological characteristics of network were analyzed.Key gene set was found by betweenness centrality and degree ranking,and function modules were identified by MCODE plug-in.ClusterProfiler package from R software was used to perform GO and KEGG enrichment analysis.lncRNAs related to diseases were found to construct lncRNA-gene interaction network.Results:SSN contained 372 nodes which represent union of disease-related genes and 470 edges which represent interactions of gene pairs.Key gene set consists of 10 genes:CREB3L1,REL,MUC1,TRAF2,LCN2,IKZF3,PIN1,PFDN5,TRIM27 and GEM.Two functional modules were found by MCODE plug-in.GO analysis showed that M1 module was enriched in CXCR chemokine receptor binding,cytokine receptor binding and other molecular functions,while M2 module was enriched in CARD domain binding,ubiquitin-protein transferase regulatory activity,etc..lncRNA-gene interaction network was built.Conclusion:Key gene set,functional modules and lncRNA-gene interaction network derived from SSN enrich understanding of molecular pathological link between SLE and SSc,and provide a reliable research perspective for further exploring pathological mechanism and intervention targets of SSc-SLE overlap syndrome.