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支气管哮喘中差异表达基因的探索与生物信息学分析

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

作者信息

Zhang M Y, Ren W, Chen S S, Zhang Q, Li C X, Wan J X, Lin J T

机构信息

Graduate School of Peking Union Medical College, Beijing 100730, China.

Department of Respiratory, Aero Space Center Hospital, Beijing 100039, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2021 Dec 14;101(46):3809-3813. doi: 10.3760/cma.j.cn112137-20210607-01293.

Abstract

To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

摘要

筛选支气管哮喘的核心差异表达基因并进行生物信息学分析。从基因表达数据库(GEO)下载哮喘患者的巨噬细胞微阵列数据GSE22528。该数据集包含来自10个人肺泡灌洗样本的转录组信息,其中5个来自过敏性哮喘患者,5个来自对照受试者。使用R 4.0.4软件筛选差异表达基因(DEGs)。利用DAVID 6.8数据库进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析以选择DEGs。使用STRING在线数据库从DEGs编码的蛋白质构建蛋白质相互作用网络(PPI)。使用Cytoscape软件构建核心模块并确定核心DEGs。肺泡灌洗样本均采集自加拿大白人,年龄范围分别为(20, 37)岁和(18, 36)岁,每组包括3名男性。在哮喘患者中,449个基因上调,47个基因下调。GO分析表明,哮喘患者中上调的基因主要参与对折叠蛋白的反应等生物学过程,分子功能集中在折叠蛋白和生长因子的结合上。下调的基因主要参与组蛋白去乙酰化和泛素介导的蛋白质降解等生物学过程,其分子功能集中在组蛋白去乙酰化活性上。KEGG通路富集分析表明,通路主要由上调基因富集,涉及Hippo信号通路、肥厚性心肌病、雌激素信号通路、致心律失常性右心室心肌病、基底细胞癌、神经激活受体配体相互作用、扩张型心肌病以及黏附与连接信号通路。通过PPI分析获得了两个核心模块,筛选出14个核心DEGs。它们是促黑素浓缩激素(PMCH)、前阿片促黑皮素原(PNOC)、鞘氨醇-1-磷酸受体2(S1PR2)、鞘氨醇-1-磷酸受体5(S1PR5)、CC型趋化因子配体21(CCL21)、 Kelch样蛋白25(KLHL25)、泛素结合酶E2V2(UBE2V2)、F-box蛋白17(FBXO17)、味觉受体2型成员3(TAS2R3)、生长抑素受体2(SSTR2)、代谢型谷氨酸受体2(GRM2)、李斯特E3泛素蛋白连接酶1(LTN1)、LIM结构域特异性蛋白7(LMO7)和环指蛋白19A基因(RNF19A),其中LTN1和UBE2V2下调,其余上调。在哮喘和对照个体的巨噬细胞中发现了DEGs。PMCH、PNOC、S1PR2、S1PR5和CCL21可能是哮喘病理过程中的核心基因。

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