Application of weighted gene co-expression network analysis to identify the hub genes in H1N1.

International journal of physiology, pathophysiology and pharmacology Pub Date : 2021-06-15 eCollection Date: 2021-01-01
Bo Sun, Xiang Guo, Xue Wen, Yun-Bo Xie, Wei-Hua Liu, Gui-Fen Pang, Lin-Ying Yang, Qing Zhang
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Abstract

Objective: Identifying the disease-associated interactions between different genes helps us to find novel therapeutic targets and predictive biomarkers.

Methods: Gene expression data GSE82050 from H1N1 and control human samples were acquired from the NCBI GEO database. Highly co-expressed genes were grouped into modules. Through Person's correlation coefficient calculation between the module and clinical phenotype, notable modules were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted, and the hub genes within the module of interest were identified. Also, gene expression data GSE27131 were acquired from the GEO database to verify differential key gene expression analysis. The CIBERSORT was used to evaluate the immune cells infiltration and the GSVA was performed to identify the differentially regulated pathways in H1N1. The receiver operating characteristic (ROC) curves were used to assess the diagnostic values of the hub genes.

Result: The black module was shown to have the highest correlation with the clinical phenotype, mainly functioning in the signaling pathways such as the mitochondrial inner membrane, DNA conformation change, DNA repair, and cell cycle phase transition. Through analysis of the black module, we found 5 genes that were highly correlated with the H1N1 phenotype. The H1N1 project from GSE27131 confirmed an increased expression of these genes.

Conclusion: By using the WGCNA we analyzed and predicted the key genes in H1N1. BRCA1, CDC20, MAD2L1, MCM2, and UBE2C were found to be the most relevant genes, which may be therapeutic targets and predictive biomarkers for H1N1 therapy.

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加权基因共表达网络分析在甲型H1N1流感中心基因鉴定中的应用。
目的:确定不同基因之间的疾病相关相互作用有助于我们寻找新的治疗靶点和预测性生物标志物。方法:从NCBI GEO数据库中获取H1N1和对照人样本GSE82050基因表达数据。高共表达基因被分组成模块。通过计算模块与临床表型之间的Person相关系数,找出显著模块。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)途径分析,确定了感兴趣模块内的枢纽基因。同时,从GEO数据库中获取基因表达数据GSE27131,验证差异关键基因表达分析。采用CIBERSORT评估免疫细胞浸润,采用GSVA鉴定H1N1的差异调控途径。采用受试者工作特征(ROC)曲线评价枢纽基因的诊断价值。结果:黑色模块与临床表型相关性最高,主要参与线粒体内膜、DNA构象改变、DNA修复、细胞周期相变等信号通路。通过对黑色模块的分析,我们发现了5个与H1N1表型高度相关的基因。来自GSE27131的H1N1项目证实了这些基因的表达增加。结论:利用WGCNA分析和预测了甲型H1N1流感的关键基因。BRCA1、CDC20、MAD2L1、MCM2和UBE2C是最相关的基因,它们可能是H1N1治疗的治疗靶点和预测性生物标志物。
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