儿童腺病毒感染基因表达谱分析及中药预测研究

Study on differentially expressed genes and Chinese medicine prediction of adenovirus infection in children

目的:通过分析腺病毒(HAdV)感染儿童与健康儿童的基因表达差异,探讨感染发生发展的机制,进而预测抗HAdV的潜在中药。方法:从GEO数据库中下载GSE68004基因芯片数据,使用NetworkAnalyst在线数据库获得差异基因(DEGs),通过STRING数据库、Cytoscape 3.7.2软件及其插件进行网络拓扑分析获得核心基因,对DEGs进行GO功能富集和KEGG通路富集分析。最后,利用CMap数据库及TCMSP、TCMID、ETCM数据库预测治疗儿童HAdV感染的潜在活性成分及中药。结果:共发现380个DEGs,以Degree值>平均值为原则,筛选出98个重要DEGs用作后续分析,包括92个上调基因和6个下调基因。筛选所得10个核心基因为CDC20、BUB1、CDC45、CDCA8、CCNB2、AURKA、TOP2A、KIF4A、UBE2C、BIRC5。富集分析结果表明,儿童HAdV感染DEGs主要涉及细胞周期通路及病毒感染相关通路。白屈菜是治疗儿童HAdV感染最有潜力的中药,血根碱是其抗HAdV的关键活性成分。结论:HAdV的关键致病靶点与细胞周期、有丝分裂、DNA复制、病毒在细胞内转运等过程有关。白屈菜及其所含的血根碱对于儿童HAd V感染的治疗具有很大的研究价值。

Objective: By analyzing the gene expression differences between adenovirus(HAdV) infected children and healthy children, to explore the mechanism of infection and then to predict the potential anti-HAdV Chinese medicine. Methods:The GSE68004 gene expression profile was downloaded from GEO database, and the differentially expressed genes(DEGs)were analyzed by NetworkAnalyst online database. DEGs were conducted network topology analysis through STRING database,Cytoscape 3.7.2 software and its plug-ins to obtain core genes, and were conducted GO function enrichment and KEGG pathway enrichment analysis. Finally, CMap database and TCMSP, TCMID, ETCM database were used to predict the potential active components and Chinese medicine for the treatment of adenovirus infection in children. Results: A total of 380 DEGs were found.Based on the principle of Degree>average, 98 important DEGs were screened for follow-up analysis, including 92 up-regulated genes and 6 down-regulated genes. The 10 core genes were CDC20, BUB1, CDC45, CDCA8, CCNB2, AURKA, TOP2A, KIF4A,UBE2C, BIRC5. The results of enrichment analysis showed that DEGs mainly involved in cell cycle pathway and virus infection related pathway. Celandine was the most potential Chinese medicine for the treatment of adenovirus infection in children, and sanguinarine was the key active component. Conclusion: The key pathogenic targets of HAdV are associated with processes such as cell cycle, mitosis, DNA replication, and viral intracellular transport. Celandine and its sanguinarine have great research values for the treatment of adenovirus infection in children.