結(jié)核病潛在關(guān)鍵基因的生物信息學(xué)分析
發(fā)布時(shí)間：2021-08-01 08:18
目的通過(guò)生物信息學(xué)方法篩選結(jié)核病的關(guān)鍵基因,為結(jié)核病的防治及科研提供新的研究方向和思路。方法分析GEO（Gene Expression Omnibus）數(shù)據(jù)庫(kù)的兩個(gè)系列微陣列數(shù)據(jù)集（GSE19443和GSE19444）,使用在線工具GEO2R來(lái)獲取結(jié)核病患者和健康對(duì)照組間的差異表達(dá)基因（differentially expressed genes,DEGs）。然后對(duì)差異表達(dá)基因進(jìn)行基因本體論分析（Gene Ontology,GO）和京都基因與基因組百科全書相關(guān)富集通路分析（Kyoto Encyclopedia of Genes and Genomes,KEGG）,通過(guò)構(gòu)建蛋白-蛋白互作（Protein-protein interaction,PPI）網(wǎng)絡(luò)來(lái)篩選出在結(jié)核病的發(fā)生發(fā)展中起著較為重要的關(guān)鍵基因及其潛在的病理機(jī)制,使用Cytoscape軟件的Genemania插件進(jìn)一步重預(yù)測(cè)差異基因的潛在的功能。結(jié)果經(jīng)過(guò)GEO2R分析后,一共獲得143個(gè)與結(jié)核病相關(guān)的差異表達(dá)基因,其中包含48個(gè)表達(dá)上調(diào)基因和50個(gè)表達(dá)下調(diào)基因;GO和KEGG分析表明,上調(diào)的差異表達(dá)基因與癌癥和系統(tǒng)發(fā)育相關(guān),而...
【文章來(lái)源】：中國(guó)病原生物學(xué)雜志. 2020,15(06)北大核心CSCD
【文章頁(yè)數(shù)】：7 頁(yè)
【部分圖文】：
GeneMania重預(yù)測(cè)關(guān)鍵基因的蛋白互作網(wǎng)絡(luò)
為了搜索差異表達(dá)基因的功能,使用DAVID數(shù)據(jù)庫(kù)分析差異表達(dá)基因?qū)?huì)在GO和KEGG哪些方面上富集,其中GO分析為生物過(guò)程(biological process, BP)、細(xì)胞組分(cell component, CC)和分子功能(molecular function, MF)。將所有上調(diào)和下調(diào)的差異表達(dá)基因分別上傳到DAVID數(shù)據(jù)庫(kù)并進(jìn)行分析,在GO結(jié)果中,上調(diào)的差異表達(dá)基因在生物過(guò)程、細(xì)胞組分和分子功能上0得到富集,其中生物過(guò)程包括腎單位發(fā)育(nephron development)、腎臟發(fā)育(kidney development)、腎臟系統(tǒng)發(fā)育(renal system development)、泌尿生殖系統(tǒng)發(fā)育(urogenital system development)以及腎單位上皮發(fā)育(nephron epithelium development)等,而細(xì)胞組分僅包括細(xì)胞頂端部分(apical part of cell),分子功能僅在結(jié)構(gòu)分子活性(structural molecule activity)和轉(zhuǎn)錄輔因子活性(transcription cofactor activity)方面差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。下調(diào)基因在生物過(guò)程和分子功能上得到富集,且主要富集在細(xì)胞組分上,生物過(guò)程包括先天免疫反應(yīng)(transcription cofactor activity)、防御反應(yīng)(defense response)、對(duì)干擾素-γ的反應(yīng)(response to interferon-gamma)、對(duì)細(xì)胞因子的反應(yīng)(response to cytokine)、免疫反應(yīng)(immune response)等;分子功能包括寡腺苷酸合成酶活性(oligoadenylate synthetase activity)、腺苷酰轉(zhuǎn)移酶活性(adenylyltransferase activity)、雙鏈RNA結(jié)合(double-stranded RNA binding)、三磷酸鳥苷結(jié)合(GTP binding)等。細(xì)胞組分的富集兩組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),因此不認(rèn)為下調(diào)的差異基因在細(xì)胞組分上富集(表2)。在KEGG結(jié)果中,表達(dá)上調(diào)的差異基因富集在與癌癥、粘著斑、Ras信號(hào)通路及阿米巴病等相關(guān)的通路上,而下調(diào)的5個(gè)差異基因(SOCS3、OAS3、OAS1、OAS2、STAT1)同時(shí)富集在相同的3條與感染性疾病相關(guān)的生物通路上(表3)。表2 差異表達(dá)基因的GO分析Table 2 GO analysis of differentially expressed genes 基因分類Gene category GO分類GO category ID及名稱ID and names 基因數(shù)Count of genes P值P value 基因Gene 上調(diào) BP GO:0072006～nephron development 5 2.97E-04 MAGI2, LAMA5, HOXA11, TEK, CTNNB1 BP GO:0001822～kidney development 6 3.76E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0072001～renal system development 6 4.91E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0001655～urogenital system development 6 8.56E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0072009～nephron epithelium development 4 0.00221307 MAGI2, LAMA5, HOXA11, CTNNB1 CC GO:0045177～apical part of cell 4 0.044370181 HPN, SORBS2, TEK, CTNNB1 MF GO:0005198～structural molecule activity 6 0.045208057 RPS26, MAGI2, LAMA5, SORBS2, RPS26P11, COL4A5 MF GO:0003712～transcription cofactor activity 5 0.049206991 RBPMS, USP21, RUNX1T1, ID3, CTNNB1 下調(diào) BP GO:0045087～innate immune response 17 4.48E-11 GBP5, SOCS3, OAS3, OAS1, OAS2, SLAMF7, STAT1, C1QC, AIM2,GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 BP GO:0006952～defense response 19 4.50E-09 GBP5, SOCS3, OAS3, OAS1, IFI44L, OAS2, SLAMF7, STAT1, C1QC,SP140, AIM2, GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 BP GO:0034341～response to interferon-gamma 9 4.68E-09 GBP5, SOCS3, FCGR1B, OAS3, OAS1, OAS2, STAT1, GBP1, GCH1 BP GO:0034097～response to cytokine 14 3.43E-08 IFI27, GBP5, PARP9, SOCS3, FCGR1B, OAS3, OAS1, OAS2, XAF1,STAT1, GAS6, AIM2, GBP1, GCH1 BP GO:0006955～immune response 18 4.74E-08 GBP5, SOCS3, OAS3, OAS1, OAS2, SLAMF7, STAT1, C1QC, AIM2,GAS6, GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 MF GO:0001730～2"-5"-oligoadenylate synthetase activity 3 3.51E-05 OAS3, OAS1, OAS2 MF GO:0070566～adenylyltransferase activity 3 0.001566 OAS3, OAS1, OAS2 MF GO:0003725～double-stranded RNA binding 3 0.011076 OAS3, OAS1, OAS2 MF GO:0005525～GTP binding 5 0.014158 GBP5, IFI44L, GBP4, GBP1, GCH1 MF GO:0032561～guanyl ribonucleotide binding 5 0.016904031 GBP5, IFI44L, GBP4, GBP1, GCH1 注:BP表示生物過(guò)程;CC表示細(xì)胞組分;MF表示分子功能。Notes: BP, biological process; cc, cell component; MF, molecular function.
將所有的差異表達(dá)基因上傳到STRING數(shù)據(jù)庫(kù)并獲得PPI網(wǎng)絡(luò)數(shù)據(jù),將PPI網(wǎng)絡(luò)數(shù)據(jù)導(dǎo)進(jìn)Cytoscape軟件進(jìn)一步分析PPI網(wǎng)絡(luò)圖潛在的生物信息(圖2)。經(jīng)過(guò)分析后確定連接度前十的基因,分別是信號(hào)轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子1(STAT1)(連接度為35分)、鳥苷酸結(jié)合蛋白5(GBP5,26分)、2"-5"-寡腺苷酸合成酶1(OAS1,25分)、連環(huán)蛋白β1(CTNNB1,25分)、鳥苷酸結(jié)合蛋白1(GBP1,25分)、2"-5"-寡腺苷酸合成酶2(OAS2, 23分)、poly(ADP-ribose)聚合酶家族成員9(PARP9,21分)、干擾素誘導(dǎo)蛋白44類似物(IFI44, 20分)、XIAP相關(guān)因子1(XAF1,19分)、細(xì)胞因子信號(hào)傳導(dǎo)抑制因子3(SOCS3,19分)。由于鳥苷酸結(jié)合蛋白4(GBP4 ,19分)和胸部上皮間質(zhì)相互作用蛋白1(EPSTI1,19分)的連接度與XAF1相同,因此共選出12個(gè)與結(jié)核病相關(guān)的關(guān)鍵基因。除鳥苷酸結(jié)合蛋白1(GBP1)外,選出的關(guān)鍵基因在結(jié)核病組中表達(dá)均下調(diào)(表4)。表4 關(guān)鍵基因Table 4 Key genes 基因Genes 基因描述Genes description 連接度(分)Connective degree 上調(diào)/下調(diào)Up/Down STAT1 signal transducer and activator of transcription 1 35 下調(diào) GBP5 guanylate binding protein 5 26 下調(diào) OAS1 2"-5"-oligoadenylate synthetase 1 25 下調(diào) CTNNB1 catenin beta 1 25 下調(diào) GBP1 guanylate binding protein 1 25 上調(diào) OAS2 2"-5"-oligoadenylate synthetase 2 23 下調(diào) PARP9 poly(ADP-ribose) polymerase family member 9 21 下調(diào) IFI44 interferon induced protein 44 like 20 下調(diào) XAF1 XIAP associated factor 1 19 下調(diào) SOCS3 suppressor of cytokine signaling 3 19 下調(diào) GBP4 guanylate binding protein 4 19 下調(diào) EPSTI1 epithelial stromal interaction 1 (breast) 19 下調(diào)
本文編號(hào)：3315155
【文章來(lái)源】：中國(guó)病原生物學(xué)雜志. 2020,15(06)北大核心CSCD
【文章頁(yè)數(shù)】：7 頁(yè)
【部分圖文】：
GeneMania重預(yù)測(cè)關(guān)鍵基因的蛋白互作網(wǎng)絡(luò)
為了搜索差異表達(dá)基因的功能,使用DAVID數(shù)據(jù)庫(kù)分析差異表達(dá)基因?qū)?huì)在GO和KEGG哪些方面上富集,其中GO分析為生物過(guò)程(biological process, BP)、細(xì)胞組分(cell component, CC)和分子功能(molecular function, MF)。將所有上調(diào)和下調(diào)的差異表達(dá)基因分別上傳到DAVID數(shù)據(jù)庫(kù)并進(jìn)行分析,在GO結(jié)果中,上調(diào)的差異表達(dá)基因在生物過(guò)程、細(xì)胞組分和分子功能上0得到富集,其中生物過(guò)程包括腎單位發(fā)育(nephron development)、腎臟發(fā)育(kidney development)、腎臟系統(tǒng)發(fā)育(renal system development)、泌尿生殖系統(tǒng)發(fā)育(urogenital system development)以及腎單位上皮發(fā)育(nephron epithelium development)等,而細(xì)胞組分僅包括細(xì)胞頂端部分(apical part of cell),分子功能僅在結(jié)構(gòu)分子活性(structural molecule activity)和轉(zhuǎn)錄輔因子活性(transcription cofactor activity)方面差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。下調(diào)基因在生物過(guò)程和分子功能上得到富集,且主要富集在細(xì)胞組分上,生物過(guò)程包括先天免疫反應(yīng)(transcription cofactor activity)、防御反應(yīng)(defense response)、對(duì)干擾素-γ的反應(yīng)(response to interferon-gamma)、對(duì)細(xì)胞因子的反應(yīng)(response to cytokine)、免疫反應(yīng)(immune response)等;分子功能包括寡腺苷酸合成酶活性(oligoadenylate synthetase activity)、腺苷酰轉(zhuǎn)移酶活性(adenylyltransferase activity)、雙鏈RNA結(jié)合(double-stranded RNA binding)、三磷酸鳥苷結(jié)合(GTP binding)等。細(xì)胞組分的富集兩組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),因此不認(rèn)為下調(diào)的差異基因在細(xì)胞組分上富集(表2)。在KEGG結(jié)果中,表達(dá)上調(diào)的差異基因富集在與癌癥、粘著斑、Ras信號(hào)通路及阿米巴病等相關(guān)的通路上,而下調(diào)的5個(gè)差異基因(SOCS3、OAS3、OAS1、OAS2、STAT1)同時(shí)富集在相同的3條與感染性疾病相關(guān)的生物通路上(表3)。表2 差異表達(dá)基因的GO分析Table 2 GO analysis of differentially expressed genes 基因分類Gene category GO分類GO category ID及名稱ID and names 基因數(shù)Count of genes P值P value 基因Gene 上調(diào) BP GO:0072006～nephron development 5 2.97E-04 MAGI2, LAMA5, HOXA11, TEK, CTNNB1 BP GO:0001822～kidney development 6 3.76E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0072001～renal system development 6 4.91E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0001655～urogenital system development 6 8.56E-04 MAGI2, LAMA5, HOXA11, TEK, ID3, CTNNB1 BP GO:0072009～nephron epithelium development 4 0.00221307 MAGI2, LAMA5, HOXA11, CTNNB1 CC GO:0045177～apical part of cell 4 0.044370181 HPN, SORBS2, TEK, CTNNB1 MF GO:0005198～structural molecule activity 6 0.045208057 RPS26, MAGI2, LAMA5, SORBS2, RPS26P11, COL4A5 MF GO:0003712～transcription cofactor activity 5 0.049206991 RBPMS, USP21, RUNX1T1, ID3, CTNNB1 下調(diào) BP GO:0045087～innate immune response 17 4.48E-11 GBP5, SOCS3, OAS3, OAS1, OAS2, SLAMF7, STAT1, C1QC, AIM2,GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 BP GO:0006952～defense response 19 4.50E-09 GBP5, SOCS3, OAS3, OAS1, IFI44L, OAS2, SLAMF7, STAT1, C1QC,SP140, AIM2, GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 BP GO:0034341～response to interferon-gamma 9 4.68E-09 GBP5, SOCS3, FCGR1B, OAS3, OAS1, OAS2, STAT1, GBP1, GCH1 BP GO:0034097～response to cytokine 14 3.43E-08 IFI27, GBP5, PARP9, SOCS3, FCGR1B, OAS3, OAS1, OAS2, XAF1,STAT1, GAS6, AIM2, GBP1, GCH1 BP GO:0006955～immune response 18 4.74E-08 GBP5, SOCS3, OAS3, OAS1, OAS2, SLAMF7, STAT1, C1QC, AIM2,GAS6, GCH1, C1QB, IFI27, PARP9, FCGR1B, XAF1, SSC5D, GBP1 MF GO:0001730～2"-5"-oligoadenylate synthetase activity 3 3.51E-05 OAS3, OAS1, OAS2 MF GO:0070566～adenylyltransferase activity 3 0.001566 OAS3, OAS1, OAS2 MF GO:0003725～double-stranded RNA binding 3 0.011076 OAS3, OAS1, OAS2 MF GO:0005525～GTP binding 5 0.014158 GBP5, IFI44L, GBP4, GBP1, GCH1 MF GO:0032561～guanyl ribonucleotide binding 5 0.016904031 GBP5, IFI44L, GBP4, GBP1, GCH1 注:BP表示生物過(guò)程;CC表示細(xì)胞組分;MF表示分子功能。Notes: BP, biological process; cc, cell component; MF, molecular function.
將所有的差異表達(dá)基因上傳到STRING數(shù)據(jù)庫(kù)并獲得PPI網(wǎng)絡(luò)數(shù)據(jù),將PPI網(wǎng)絡(luò)數(shù)據(jù)導(dǎo)進(jìn)Cytoscape軟件進(jìn)一步分析PPI網(wǎng)絡(luò)圖潛在的生物信息(圖2)。經(jīng)過(guò)分析后確定連接度前十的基因,分別是信號(hào)轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子1(STAT1)(連接度為35分)、鳥苷酸結(jié)合蛋白5(GBP5,26分)、2"-5"-寡腺苷酸合成酶1(OAS1,25分)、連環(huán)蛋白β1(CTNNB1,25分)、鳥苷酸結(jié)合蛋白1(GBP1,25分)、2"-5"-寡腺苷酸合成酶2(OAS2, 23分)、poly(ADP-ribose)聚合酶家族成員9(PARP9,21分)、干擾素誘導(dǎo)蛋白44類似物(IFI44, 20分)、XIAP相關(guān)因子1(XAF1,19分)、細(xì)胞因子信號(hào)傳導(dǎo)抑制因子3(SOCS3,19分)。由于鳥苷酸結(jié)合蛋白4(GBP4 ,19分)和胸部上皮間質(zhì)相互作用蛋白1(EPSTI1,19分)的連接度與XAF1相同,因此共選出12個(gè)與結(jié)核病相關(guān)的關(guān)鍵基因。除鳥苷酸結(jié)合蛋白1(GBP1)外,選出的關(guān)鍵基因在結(jié)核病組中表達(dá)均下調(diào)(表4)。表4 關(guān)鍵基因Table 4 Key genes 基因Genes 基因描述Genes description 連接度(分)Connective degree 上調(diào)/下調(diào)Up/Down STAT1 signal transducer and activator of transcription 1 35 下調(diào) GBP5 guanylate binding protein 5 26 下調(diào) OAS1 2"-5"-oligoadenylate synthetase 1 25 下調(diào) CTNNB1 catenin beta 1 25 下調(diào) GBP1 guanylate binding protein 1 25 上調(diào) OAS2 2"-5"-oligoadenylate synthetase 2 23 下調(diào) PARP9 poly(ADP-ribose) polymerase family member 9 21 下調(diào) IFI44 interferon induced protein 44 like 20 下調(diào) XAF1 XIAP associated factor 1 19 下調(diào) SOCS3 suppressor of cytokine signaling 3 19 下調(diào) GBP4 guanylate binding protein 4 19 下調(diào) EPSTI1 epithelial stromal interaction 1 (breast) 19 下調(diào)
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