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Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses
medRxiv - Genetic and Genomic Medicine Pub Date : 2020-12-24 , DOI: 10.1101/2020.12.21.20248688
Basavaraj Vastrad , Chanabasayya Vastrad , Iranna Kotturshetti

Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. Pathway and GO enrichment analyses of DEGs were performed. Furthermore, the protein -protein interaction (PPI) network was predicted using the IntAct Molecular Interaction Database and visualized with Cytoscape software. In addition, hub genes and important modules were selected based on the network. Finally, we constructed target genes - miRNA regulatory network and target genes - TF regulatory network. Hub genes were validated. A total of 891 DEGs 448 of these DEGs presented significant up regulated, and the remaining 443 down regulated were obtained. Pathway enrichment analysis indicated that up regulated genes were mainly linked with glutamine degradation/glutamate biosynthesis, while the down regulated genes were involved in melatonin degradation. GO enrichment analyses indicated that up regulated genes were mainly linked with chemical synaptic transmission, while the down regulated genes were involved in regulation of immune system process. hub and target genes were selected from the PPI network, modules, and target genes - miRNA regulatory network and target genes - TF regulatory network namely YWHAZ, GABARAPL1, EZR, CEBPA, HSPB8, TUBB2A and CDK14. The current study sheds light on the molecular mechanisms of sCJD and may provide molecular targets and diagnostic biomarkers for sCJD.

中文翻译:

基于综合生物信息学分析鉴定与散发性克雅氏病相关的潜在关键基因和途径

偶发性Creutzfeldt-Jakob病(sCJD)是神经退行性疾病,也称为called病毒病,与预后不良相关。当前研究的目的是阐明sCJD的潜在分子机制。从基因表达综合数据库下载了mRNA微阵列数据集GSE124571。筛选差异表达基因(DEG)。对DEG进行了途径和GO富集分析。此外,使用IntAct分子相互作用数据库预测了蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape软件对其进行了可视化。此外,基于网络选择了中心基因和重要模块。最后,我们构建了靶基因-miRNA调控网络和靶基因-TF调控网络。Hub基因已得到验证。这些DEG中共有891个DEG,其中448个存在上调,而其余443个下调。通路富集分析表明,上调的基因主要与谷氨酰胺降解/谷氨酸的生物合成有关,而下调的基因与褪黑激素的降解有关。GO富集分析表明,上调的基因主要与化学突触传递有关,而下调的基因则参与了免疫系统过程的调节。中心和靶基因选自PPI网络,模块和靶基因-miRNA调控网络和靶基因-TF调控网络,即YWHAZ,GABARAPL1,EZR,CEBPA,HSPB8,TUBB2A和CDK14。
更新日期:2020-12-24
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