Rezaei-Tavirani Sina, Asri Nastaran, Emamhadi MohammadAli, Jahani-Sherafat Somayeh, Seyed Salehi Ali, Gholamrezaei Zahra, Lak Elena
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gastroenterol Hepatol Bed Bench. 2020 Winter;13(Suppl1):S53-S59.
This study was aimed at gene assessment of Crohn's disease (CD) through protein-protein interaction (PPI) network analysis to find crucial genes.
CD is a major subtype of inflammatory bowel diseases (IBD), which affects gastrointestinal tract. PPI network analysis is a suitable tool to clarify a critical gene as a drug target or diagnostic biomarker for these types of diseases.
Gene expression profile GSE126124 of 20 CD patients and 20 healthy controls was obtained from the Gene Expression Omnibus (GEO) database. RNA profile of peripheral blood mononuclear cells (PBMCs) and colon biopsy samples of the studied groups was investigated. Crucial genes were selected and analyzed via the PPI network by Cytoscape software. Gene ontology enrichment for the hubs, bottlenecks, and hub-bottlenecks was performed via CluGO plugin of Cytoscape software.
Eighty-one differentially expressed genes (DEGs) among 250 initial DEGs were highlighted as significant by FC>2 and p-value ≤ 0.05, and 69 significant DEGs were used for PPI network construction. The network was characterized by poor connections, so 20 top neighbors were added to form a scale-free network. The main connected component included 39 query DEGs and 20 added first neighbors. Three clusters of biological processes associated with crucial genes were identified and discussed.
The results of this study indicated that GATA3 has a key role in CD pathogenesis and could be a possible drug target or diagnostic biomarker for Crohn's disease.
本研究旨在通过蛋白质-蛋白质相互作用(PPI)网络分析对克罗恩病(CD)进行基因评估,以寻找关键基因。
CD是炎症性肠病(IBD)的一种主要亚型,会影响胃肠道。PPI网络分析是一种用于明确关键基因作为这类疾病的药物靶点或诊断生物标志物的合适工具。
从基因表达综合数据库(GEO)中获取20例CD患者和20例健康对照的基因表达谱GSE126124。对研究组外周血单核细胞(PBMCs)和结肠活检样本的RNA谱进行了研究。通过Cytoscape软件经PPI网络选择并分析关键基因。通过Cytoscape软件的CluGO插件对中心节点、瓶颈节点和中心-瓶颈节点进行基因本体富集分析。
在250个初始差异表达基因(DEGs)中,81个差异表达基因因FC>2且p值≤0.05而被突出显示为显著基因,69个显著差异表达基因用于构建PPI网络。该网络连接性较差,因此添加了20个顶级邻居以形成无标度网络。主要连通组件包括39个查询差异表达基因和20个添加进来的一级邻居。识别并讨论了与关键基因相关的三个生物过程簇。
本研究结果表明,GATA3在CD发病机制中起关键作用,可能是克罗恩病的一个潜在药物靶点或诊断生物标志物。