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溃疡性结肠炎关键候选基因和通路的生物信息学分析。

Bioinformatics Analysis of Key Candidate Genes and Pathways in Ulcerative Colitis.

机构信息

College of Basic Medicine & Sichuan Industrial Institute of Antibiotics, Chengdu University.

Central Laboratory of Clinical Medicine, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital.

出版信息

Biol Pharm Bull. 2020;43(11):1760-1766. doi: 10.1248/bpb.b20-00488.

Abstract

Ulcerative colitis (UC) is chronic, idiopathic disease that affects the colon and the rectum and the underlying pathogenesis of UC remains to be known. The clinical drugs are mainly work based on anti-inflammation and immune system. However, most of them are expensive and have severe side effects. Therefore, identification of novel targets and exploring new drugs are urgently needed. In this study, several bioinformatics approaches were used to discover key genes and further in order to explore the pathogenesis of UC. Two microarray datasets, GSE38713 and GSE9452 were selected from NCBI-Gene Expression Omnibus database. Differentially expression genes (DEGs) were identified by using LIMMA Package of R. Then, we filtered clustered candidate genes into Gene Ontology (GO) and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery (DAVID), KEGG pathway based on functions and signaling pathways with significant enrichment analysis. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) analysis, and visualized by Cytoscape and further analyzed by Molecular Complex Detection. Lastly, 353 up-regulated and 145 down-regulated genes were than recognized. After consulting a number of references and network degree analysis, four hub genes, namely FCGR2A, C3, INPP5A, and ACAA1 were identified, and these genes were mainly enriched in complement and coagulation cascades, mineral absorption, and Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathways. In conclusion, this study would provide new clues for the pathogenesis and identification of drug targets of UC in the near future.

摘要

溃疡性结肠炎(UC)是一种慢性、特发性疾病,影响结肠和直肠,UC 的潜在发病机制尚不清楚。临床药物主要基于抗炎和免疫系统起作用。然而,大多数药物昂贵且副作用严重。因此,迫切需要识别新的靶点和探索新的药物。在这项研究中,使用了几种生物信息学方法来发现关键基因,并进一步探索 UC 的发病机制。从 NCBI-Gene Expression Omnibus 数据库中选择了两个微阵列数据集 GSE38713 和 GSE9452。使用 R 中的 LIMMA 包鉴定差异表达基因(DEGs)。然后,我们将聚类候选基因过滤成基因本体论(GO)和通路富集分析与数据库用于注释、可视化和综合发现(DAVID),基于功能和信号通路的 KEGG 通路与显著富集分析。蛋白质-蛋白质相互作用(PPI)网络通过搜索工具检索相互作用基因/蛋白质(STRING)分析构建,并用 Cytoscape 可视化,并进一步通过分子复合物检测进行分析。最后,识别出 353 个上调基因和 145 个下调基因。在查阅了大量参考文献和网络度分析后,确定了 4 个关键基因,即 FCGR2A、C3、INPP5A 和 ACAA1,这些基因主要富集在补体和凝血级联、矿物质吸收和过氧化物酶体增殖物激活受体(PPAR)信号通路中。总之,这项研究将为 UC 的发病机制和药物靶点的识别提供新的线索。

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