利用加权基因共表达网络分析识别胆道闭锁相关的枢纽基因

目的:通过加权基因共表达网络分析（WGCNA）识别胆道闭锁（BA）发病相关的枢纽基因。方法:从基因表达汇编（GEO）数据库下载BA基因芯片数据集GSE46960，利用WGCNA构建基因共表达网络，识别与BA相关的模块与枢纽基因，对关键模块进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。结果:通过WGCNA分析构建了20个基因共表达模块，确定与BA显著相关的模块为黄色模块（r=0.69，P＜0.05），将黄色模块中的基因按基因连通性及基因显著性的不同阈值进一步筛选出16个枢纽基因。对黄色模块进行GO及KEGG分析显示，与BA显著相关的基因主要富集在细胞外基质（ECM）、细胞黏附分子、色氨酸代谢、甘油磷脂代谢、过氧化物酶体增殖物激活受体（PPAR）信号通路。结论:利用WGCNA方法识别出与BA相关的关键模块和16个枢纽基因，其中新发现有12个基因可能与BA发病相关，可能帮助阐明BA发病的机制。

Identification of hub genes in biliary atresia by weighted gene co-expression network analysis

Objective:To identify hub genes related to the pathogenesis of biliary atresia（BA） by weighted gene co-expression network analysis（WGCNA）. Methods:The BA gene chip dataset GSE46960 was downloaded from the Gene Expression Omnibus （GEO） database，and the gene co-expression network was constructed by WGCNA. The modules and hub genes related to biliary atresia were screened out，and the key module were analyzed by Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）. Results:Twenty gene co-expression modules were constructed through WGCNA，and the module related to biliary atresia were identified as yellow modules（r=0.69，P＜0.05）. The genes in the yellow module were further screened for 16 hub genes according to different thresholds of gene connectivity and gene significance. The results of GO and KEGG analysis on yellow module genes showed that genes significantly associated with biliary atresia were mainly enriched in extracellular matrix，cell adhesion molecules，tryptophan metabolism，glycerophospholipid metabolism and PPAR signaling pathway. Conclusion:WGCNA method is used to identify the key modules and 16 hub genes related to biliary atresia，of which 12 genes may be related to the pathogenesis of biliary atresia，which may help to clarify the pathogenesis of biliary atresia.