摘要
目的:通过生物信息学分析筛选脓毒症心肌病（SCM）的关键致病基因。方法:从基因表达谱（GEO）数据库下载微阵列表达数据集GSE79962，此数据集包含因脓毒症而死亡患者及健康供体的心脏基因谱全基因组基因表达水平，使用在线GEO2R分析工具进行差异表达基因（DEGs）筛选及分析，并使用DAVID 6.8数据库对DEGs进行功能富集分析。采用STRING数据库进行蛋白质相互作用（PPI）网络分析，并使用CytoHubba筛选排名前10位的关键基因。结果:从数据集GSE79962中共筛选到228个DEGs，其中156个为上调基因，72个为下调基因。对228个DEGs进行基因本体（GO）、京都市基因与基因组百科全书（KEGG）途径富集分析，DEGs主要涉及3条GO功能注释（包含2条细胞成分途径、1条生物过程途径）及3条KEGG途径（包含代谢通路、嗅觉传导、神经内分泌腺体）。PPI网络筛选出了10个关键基因，其中5个上调基因，包括包括核仁复合体关联3同源物（NOC3L），含SDA1域1（SDAD1），补缀同源物1（PTCH1），氯氰菊酯重链（CLTC）及核因子κB激酶抑制剂β（IKBKB）；5个下调基因，包括色氨酸-天门冬氨酸重复序列（WDR4、WDR36、WDR82），跨膜卷曲螺旋结构域1（TMCO1）及Toll样受体9（TLR9）。结论:NOC3L、SDAD1、PTCH1、CLTC、IKBKB、WDR4、WDR36、WDR82、TMCO1、TLR9为SCM的关键致病基因，今后可通过深入研究这些基因，尤其是WDR基因，来进一步阐明SCM的发生发展机制。
Abstract
Objective:To screen key pathogenic genes in septic cardiomyopathy (SCM) by bioinformatics analysis.Methods:The GSE79962 dataset was downloaded from the gene expression omnibus (GEO). The dataset contained genome-wide expression levels of heart gene profiles from patients who had died of sepsis and from healthy donors. The differentially expressed genes (DEGs) were screened and analyzed using an online GEO2R analysis tool, and the functional enrichment analysis of DEGs was carried out using the DAVID 6.8 database. The protein-protein interaction (PPI) network analysis was performed using the STRING database, and the CytoHubba software was used to screen the top 10 key genes.Results:A total of 228 DEGs were identified from the GSE79962 dataset, including 156 up-regulated genes and 72 down-regulated genes. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of 228 DEGs showed that DEGs mainly involved three GO functional annotations (including two cellular component pathways and a biological process pathway) and three KEGG pathways (including a metabolic pathway, an olfactory transduction, and a neuroendocrine gland). The PPI network screened out 10 key genes, five of which were up-regulated, including nucleolar complex protein 3 homolog (NOC3L), SDA1 domain containing 1 (SDAD1), patched 1 (PTCH1), clathrin heavy chain (CLTC), and inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), and five of which were down-regulated, including WD repeat domains (WDR4, WDR36, and WDR82), transmembrane and coiled-coil domains 1 (TMCO1), and Toll like receptor 9 (TLR9).Conclusion:NOC3L, SDAD1, PTCH1, CLTC, IKBKB, WDR4, WDR36, WDR82, TMCO1, and TLR9 are key pathogenic genes of SCM, and in-depth study of these genes, especially family of WDR genes, can be conducted to further clarify the occurrence and development mechanism of SCM.
万方数据