生物信息学技术筛选微小病变肾病差异表达基因及其作用通路分析

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目的:筛选微小病变肾病(minimal change disease,MCD)的差异表达基因及其作用通路,探讨MCD发病的分子机制。方法:芯片数据来源于美国国立生物技术信息中心(NCBI)平台下的基因表达综合数据库(GEO)。选取含MCD信息的数据芯片GSE104948和GSE104954,数据集包含19例MCD肾活检组织和36例正常对照肾组织的基因表达阵列数据。利用生物信息学方法分析基因芯片数据,使用在线工具GEO2R分析数据及筛选差异表达基因,通过DAVID 6.8数据库对差异表达基因进行GO和KEGG功能富集分析,以及参与代谢通路基因之间的网络分析。用String 11.0数据库和Cytoscape 3.7.2软件分析MCD差异表达基因之间的关系,以及对基因之间进行可视化分析。采用Cyto Hubba插件分析蛋白质相互作用网络的关联度,筛选关键表达基因。结果:用在线工具GEO2R共筛选出MCD患者302个高表达的差异基因。GO分析结果显示,差异表达基因的产物多定位在细胞外基质、细胞外泌体、细胞核周等区域,发挥细胞黏附分子结合、脱氧胞苷脱氨酶活性、蛋白质二聚化活性、2'-5'-寡腺苷酸合成酶活性等功能,以及参与细胞外基质形成、细胞溶解、细胞凋亡、炎性反应和免疫反应等生物过程。KEGG分析结果显示,差异表达基因在局部黏附、NOD样受体等信号通路中富集。结合GO分析和Cyto Hubba分析结果,筛选出n PYCARD基因为诱导MCD肾脏炎性反应发生的关键基因。n 结论:炎性反应可能参与了MCD的发生发展,n PYCARD基因可能为诱发MCD炎性反应的关键基因。n “,”Objective:To identify the differentially expressed genes and pathways of minimal change disease (MCD) by bioinformatics analysis, and to explore the pathogenesis of MCD.Methods:The gene expression omnibus (GEO) under the National Center for Biotechnology Information (NCBI) platform of the United States was used, and the data chips GSE104948 and GSE104954 containing MCD information were selected. The data set contained the gene expression array data of 19 cases of MCD renal biopsy tissue and 36 cases of normal renal tissue. The online tool GEO2R was used to analyze data and screen differentially expressed genes, and DAVID 6.8 database was used to perform GO and KEGG functional enrichment analysis of differentially expressed genes and network analysis of genes involved in metabolic pathways. The String 11.0 database and Cytoscape 3.7.2 software were used to analyze the relationship between MCD differentially expressed genes and perform visual analysis. At the same time, the CytoHubba plug-in was used to analyze the degree of association of protein interaction networks and screen key expressed genes.Results:A total of 302 highly expressed differentially expressed genes were identified by online tool GEO2R. GO analysis showed that the products of these differential genes were mostly located in the extracellular matrix, exosomes, pernucleus and other regions, exerting cell adhesion molecule binding, deoxycytidine deaminase activity, protein homodimerization activity, 2'-5'-oligoadenylic acid synthase activity and other functions, as well as participating in the formation of extracellular matrix, cell lysis, cell apoptosis, inflammatory response, immune response and other biological processes. KEGG analysis showed that differentially expressed genes were enriched in local adhesion, NOD-like receptor and other signal pathways. Combining the results of GO analysis and Cyto Hubba analysis, then PYCARD gene was screened out as the key gene that induced the inflammatory response in MCD kidney.n Conclusions:The inflammatory response may be involved in the occurrence and development of MCD, and the n PYCARD gene may be a key gene in the induction of inflammatory response in MCD.n
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