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Integrative Analyses of Genes Associated with Fulminant Type 1 Diabetes
Journal of Immunology Research ( IF 3.5 ) Pub Date : 2020-10-06 , DOI: 10.1155/2020/1025857
Xiaofeng Ye 1, 2 , Tianshu Zeng 1, 2 , Wen Kong 1, 2 , Lu-Lu Chen 1, 2
Affiliation  

Objective. Fulminant type 1 diabetes (FT1D) is a type of type 1 diabetes, which is characterized by rapid onset of disease and severe metabolic disorders. We intend to screen for crucial genes and potential molecular mechanisms in FT1D in this study. Method. We downloaded GSE44314, which includes six healthy controls and five patients with FT1D, from the GEO database. Identification of differentially expressed genes (DEGs) was performed by NetworkAnalyst. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were screened by an online tool—Database for Annotation, Visualization, and Integration Discovery (DAVID). Protein-protein interaction (PPI) network and hub genes among DEGs were analyzed by NetworkAnalyst. And we also use NetworkAnalyst to find out the microRNAs (miRNAs) and transcription factors (TFs) which regulate the expression of DEGs. Result. We identified 130 DEGs (60 upregulated and 70 downregulated DEGs) between healthy controls and FT1D patients. GO analysis results revealed that DEGs were mostly enriched in generation of precursor metabolites and energy, neurohypophyseal hormone activity, and mitochondrial inner membrane. KEGG pathway analysis demonstrated that DEGs were mostly involved in nonalcoholic fatty liver disease. Results indicated that NCOA1, SRF, ERBB3, EST1, TOP1, UBE2S, INO80, COX7C, ITGAV, and COX6C were the top hub genes in the PPI network. Furthermore, we recognized that LDLR, POTEM, IFNAR2, BAZ2A, and SRF were the top hub genes in the miRNA-target gene network, and SRF, TSPAN4, CD59, ETS1, and SLC25A25 were the top hub genes in the TF-target gene network. Conclusion. Our study pinpoints key genes and pathways associated with FT1D by a sequence of bioinformatics analysis on DEGs. These identified genes and pathways provide more detailed molecular mechanisms of FT1D and may provide novel therapeutic targets.

中文翻译:

暴发性1型糖尿病相关基因的综合分析

客观。暴发性 1 型糖尿病 (FT1D) 是 1 型糖尿病的一种,其特点是发病迅速,代谢紊乱严重。我们打算在本研究中筛选 FT1D 中的关键基因和潜在的分子机制。方法. 我们从 GEO 数据库下载了 GSE44314,其中包括六名健康对照和五名 FT1D 患者。差异表达基因 (DEG) 的鉴定由 NetworkAnalyst 进行。DEGs 的基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 富集分析通过在线工具 - 注释、可视化和集成发现数据库 (DAVID) 进行筛选。通过 NetworkAnalyst 分析 DEG 之间的蛋白质-蛋白质相互作用 (PPI) 网络和中枢基因。我们还使用 NetworkAnalyst 来找出调节 DEGs 表达的 microRNAs (miRNAs) 和转录因子 (TFs)。结果. 我们在健康对照和 FT1D 患者之间确定了 130 个 DEG(60 个上调和 70 个下调的 DEG)。GO分析结果显示,DEGs主要富集前体代谢物和能量的产生、神经垂体激素活性和线粒体内膜。KEGG 通路分析表明,DEGs 主要与非酒精性脂肪肝疾病有关。结果表明,NCOA1、SRF、ERBB3、EST1、TOP1、UBE2S、INO80、COX7C、ITGAV和COX6C是PPI网络中的顶级枢纽基因。此外,我们认识到 LDLR、POTEM、IFNAR2、BAZ2A 和 SRF 是 miRNA 靶基因网络中的顶级中枢基因,而 SRF、TSPAN4、CD59、ETS1 和 SLC25A25 是 TF 靶基因中的顶级中枢基因网络。结论. 我们的研究通过对 DEG 的一系列生物信息学分析确定了与 FT1D 相关的关键基因和途径。这些确定的基因和通路提供了更详细的 FT1D 分子机制,并可能提供新的治疗靶点。
更新日期:2020-10-06
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