基于WGCNA识别IgG介导的西红柿不耐受枢纽蛋白

Identification of Hub Proteins in IgG Mediated Tomato Intolerance based on WGCNA

目的基于加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)方法识别IgG介导的西红柿不耐受相关蛋白质共表达模块及枢纽蛋白,为其发生机制研究提供依据。方法收集IgG介导的西红柿不耐受患者及健康对照血清样本,使用DIA全扫描蛋白质组学定性定量技术获得蛋白质表达数据;利用WGCNA方法构建共表达网络,识别与IgG介导的西红柿不耐受相关的模块,并进行模块GO功能注释及KEGG通路富集分析;利用Cytoscape获得IgG介导的西红柿不耐受相关模块的枢纽蛋白。结果获得IgG介导的西红柿不耐受相关的蛋白质模块两个,分别为blue模块和turquoise模块。blue模块与IgG介导的西红柿不耐受相关系数为-0.90;GO富集分析发现,该模块中蛋白主要参与脂蛋白重构、脂质代谢等相关生物过程以及蛋白质级联激活、补体激活等免疫调节过程;KEGG分析富集到5条通路,包括胆固醇代谢通路、PPAR信号通路、补体和凝血级联通路、类维生素A代谢和运输通路、维生素和辅酶因子代谢通路。turquoise模块与IgG介导的西红柿不耐受相关系数为0.72;GO富集分析发现,该模块主要与蛋白质级联激活、补体激活经典途径、体液免疫应答、受体介导的内吞,血小板脱颗粒、抗氧化活性等生物过程有关;KEGG分析富集到2条通路,补体和凝血级联通路、吞噬体通路。筛选出IgG介导的西红柿不耐受相关模块中的枢纽蛋白为APOA1、APOA4、APOC3、APOA2、APOC1、C3、HRG、FGB、HP、TF。结论WGCNA方法进行IgG介导的西红柿不耐受蛋白质表达数据分析发现:脂质、胆固醇代谢等过程的改变可能是其发生的重要环节;获得的载脂蛋白类蛋白质及其他枢纽蛋白是其潜在关键调控蛋白;本研究从系统生物学的角度,为IgG介导的西红柿不耐受发生机制探索提供了依据和研究方向。

Objective We aimed to identify the protein co-expression modules and hub proteins of IgG mediated tomato intolerance using weighted gene co-expression network analysis(WGCNA)method,and provide a basis for the study on the mechanism of IgG mediated tomato intolerance.Methods We collected serum samples of IgG mediated tomato intolerance patients and healthy controls,and used DIA full scan proteomics qualitative and quantitative technology to obtain protein expression data.WGCNA was used to identify modules related to IgG mediated tomato intolerance,which were used for GO functional annotation and KEGG pathway enrichment analysis.Finally,the hub proteins of IgG mediated tomato intolerance related modules were obtained with Cytoscape software.Results Two modules were identified as IgG mediated tomato intolerance related modules,blue module and turquoise module with the correlation coefficient of-0.90 and 0.72,respectively.GO enrichment analysis found that the proteins in blue module were mainly involved in lipoprotein remodeling,lipid metabolism and other biological processes,as well as protein cascade activation,complement activation and other immune regulatory processes;KEGG analysis found five enriched pathways,including cholesterol metabolism pathway,PPAR signaling pathway,complement and coagulation level pathway,vitamin A-like Metabolic and transport pathways,vitamin and coenzyme metabolic pathways.Go enrichment analysis of turquoise module showed that,proteins in this module were mainly related to protein cascade activation,classical complement activation pathway,humoral immune response,receptor-mediated endocytosis,platelet degranulation,antioxidant activity and other biological processes;KEGG analysis revealed two enriched pathways,complement and coagulation level pathway,phagosome pathway.ApoA1,APOA4,APOC3,apoa2,APOC1,C3,HRG,FGB,HP and TF were identified as hub proteins in IgG mediated tomato intolerance related modules.Conclusion WGCNA method analysis of IgG mediated tomato intolerance protein expression data found that,the varying of lipid and cholesterol metabolism may play a key role inIgG mediated tomato intolerance,and the obtained apolipoprotein proteins and other hub proteins are the potential key regulatory proteins of IgG mediated tomato intolerance.Our study provides a basis and direction for the exploration of the mechanism of IgG mediated tomato intolerance from the perspective of system biology.