染矽塵大鼠差異性表達(dá)基因生物信息學(xué)分析
發(fā)布時(shí)間:2018-01-21 17:21
本文關(guān)鍵詞: 矽肺 大鼠 生物信息學(xué) 基因 蛋白 出處:《中國職業(yè)醫(yī)學(xué)》2017年02期 論文類型:期刊論文
【摘要】:目的采用生物信息學(xué)方法,對染矽塵大鼠周圍血標(biāo)本的芯片進(jìn)行差異基因表達(dá)譜分析,篩選與矽肺發(fā)生發(fā)展相關(guān)的潛在差異表達(dá)基因(DEGs)和信號通路。方法從高通量基因表達(dá)數(shù)據(jù)庫檢索染矽塵大鼠的周圍血樣品基因表達(dá)微陣列芯片數(shù)據(jù)集GSE27023,采用配對樣本t檢驗(yàn)和倍比法篩選DEGs,采用DAVID數(shù)據(jù)庫進(jìn)行基因本體分析和京都基因與基因組百科全書(KEGG)通路分析,采用相互作用基因庫檢索工具和Cytoscape軟件構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用(PPI)網(wǎng)絡(luò)。結(jié)果共篩選出2 767個(gè)刺激反應(yīng)DEGs,上調(diào)基因1 363個(gè),下調(diào)基因1 404個(gè)。KEGG通路分析結(jié)果顯示,鈣信號通路、神經(jīng)活性的受體-配體相互作用通路和Ras相關(guān)蛋白1信號通路等39條信號通路被顯著富集,DEGs富集最多、最顯著的是鈣信號通路。PPI網(wǎng)絡(luò)分析篩選出節(jié)點(diǎn)度最高的前10個(gè)中心蛋白編碼基因分別是絲裂原活化蛋白激酶14(Mapk14)、DNA指導(dǎo)的RNA聚合酶Ⅱ亞基、成紅細(xì)胞白血病病毒癌基因同源物4、B淋巴細(xì)胞瘤-2基因(Bcl-2)、受體相互作用的絲氨酸/蘇氨酸激酶4、PH域富含亮氨酸重復(fù)蛋白磷酸酶2、DNA指導(dǎo)的RNA聚合酶Ⅲ亞基、神經(jīng)源性基因Notch同源蛋白1、組蛋白去乙;1、酵母交換型轉(zhuǎn)換/蔗糖不發(fā)酵相關(guān)基質(zhì)關(guān)聯(lián)肌動(dòng)蛋白依賴性調(diào)節(jié)因子亞家族A成員4,其中表達(dá)上調(diào)、節(jié)點(diǎn)度最高的是Mapk14,表達(dá)下調(diào)、節(jié)點(diǎn)度最高的是Bcl-2。結(jié)論通過再次分析大鼠染矽塵后周圍血芯片數(shù)據(jù),篩選出與大鼠染矽塵毒性反應(yīng)相關(guān)的39條信號通路和10個(gè)DEGs;鈣信號通路和基因Mapk14、Bcl-2可能在大鼠矽肺的發(fā)生發(fā)展過程中發(fā)揮重要作用。
[Abstract]:Objective to analyze the differential gene expression profile of peripheral blood samples from rats exposed to silica by bioinformatics. Screening of potential differentially expressed genes associated with the development of silicosis. Methods the microarray data sets of gene expression in peripheral blood samples of silicon-exposed rats were retrieved from the high-throughput gene expression database. DAVID database was used for gene ontology analysis and KEGG pathway analysis for Kyoto gene and genome encyclopedia. A protein-protein interaction (PPI) network was constructed by using interaction gene bank search tool and Cytoscape software. A total of 2767 stimulatory DEGs were screened. 1 363 up-regulated genes and 1 404 down-regulated genes. KEGG pathway analysis showed that calcium signaling pathway. 39 signal pathways such as receptor-ligand interaction pathway and Ras associated protein 1 signaling pathway were significantly enriched in degs. The most significant was calcium signaling pathway. PPI network analysis showed that the top 10 core protein coding genes with the highest nodal degree were mitogen-activated protein kinase 14 Mapk14). DNA directed RNA polymerase 鈪,
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