基于高通量芯片对小儿流感生物信息学分析

doi:10.3969/j.issn.1004-583X.2021.09.010

摘要/Abstract

摘要：

目的通过生物信息学工具筛选小儿流感患者的相关差异基因(differential gene, DEG),探讨小儿流感患者的核心基因并阐明其发病机制。方法从基因表达数据库(gene expression database, GEO)中下载符合本研究要求的小儿流感患者的转录组数据,采用基因分析表达工具(GEO2R)对DEGs进行筛选。采用基因本体(gene ontology, GO)分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析DEGs的功能和富集通路情况。利用STRING数据库构建蛋白互作网络(protein-protein interaction, PPI),并利用Cytoscape软件筛选核心DEGs。结果共有GSE42026、GSE29366、GSE34205、 GSE38900 4个芯片数据库纳入分析,经过分析共发现30个DEGs,29个下调,1个上调。GO分析发现DEGs主要参与Ⅰ型干扰素信号通路,细胞对Ⅰ型干扰素的反应,2'-5'-寡聚腺苷酸合成酶激活,双链RNA的结合。KEGG发现DEGs主要富集在甲型流感病毒、麻疹、丙型肝炎以及单纯疱疹病毒感染信号通路。蛋白互作分析表明,筛选出的潜在10个核心基因分别为IFIT3、MX1、OAS3、OAS2、OAS1、IFI27、IFI44、RSAD2、IFI44L、LY6E。结论以干扰素为中心的基因富集通路可能是小儿流感患者的主要发病机制,筛选出来的核心基因可能参与小儿流感的感染过程,且可能成为临床治疗的新靶点。

关键词: 流感, 人, 流感核心基因, 差异基因, 计算生物学

Abstract:

Objective To screen the related differential genes(DEGs) of pediatric influenza by bioinformatics tools, aiming to explore core genes and elucidate pathogenesis. Methods The transcriptome data of pediatric influenza that met the requirements were downloaded from gene expression omnibus(GEO) database, and DEGs were screened by gene analysis tool GEO2R. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) were analyzed for the function and enrichment pathway of DEGs. The protein-protein interaction(PPI) network was constructed by using the STRING database, and the core differential genes were selected by using Cytoscape software. Results A total of four databases (GSE42026, GSE29366, GSE34205 and GSE38900) and 30 DEGs were included in the study with 29 down regulated and 1 up regulated. GO analysis showed that DEGs were mainly involved in type I IFN signaling pathway, cell response to type I IFN, 2'-5'-oligoadenylate synthase activation and double stranded RNA binding. KEGG analysis showed that DEGs were mainly enriched in influenza A virus, measles, hepatitis C and herpes simplex virus infection signaling pathways. PPI analysis showed that the potential 10 core genes were IFIT3, MX1, OAS3, OAS2, OAS1, IFI27, IFI44, RSAD2, IFI44L and LY6E. Conclusion Interferon centered gene enrichment pathway may be the main pathogenesis for pediatric influenza. The core genes screened out may participate in the infection process of children with influenza, and become a new target for clinical treatment.

Key words: influenza, human, influenza core genes, differential gene, computational biology

中图分类号:

R511.7

金虹, 李晓岚. 基于高通量芯片对小儿流感生物信息学分析[J]. 临床荟萃, 2021, 36(9): 811-819.

Jin Hong, Li Xiaolan. Analysis of bioinformatics in pediatric influenza based on chip with high-throughput[J]. Clinical Focus, 2021, 36(9): 811-819.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.09.010

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I9/811

图/表 11

参考文献 19

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类别	项目	GO名称	基因数量	P值
BP	GO:0060337	Ⅰ型干扰素通路	14	<0.01
BP	GO:0071357	Ⅰ型干扰素的细胞反应	14	<0.01
BP	GO:0034340	Ⅰ型干扰素的应答	14	<0.01
BP	GO:0051607	对病毒的防御	14	<0.01
BP	GO:0009615	对病毒的应答	15	<0.01
BP	GO:0006952	防御反应	22	<0.01
BP	GO:0051707	对其他生物的反应	18	<0.01
BP	GO:0043207	对外界生物刺激的反应	18	<0.01
BP	GO:0009607	生物刺激反应	18	<0.01
BP	GO:0098542	对其他生物的防御反应	15	<0.01
BP	GO:0006955	免疫反应	23	<0.01
BP	GO:0045069	病毒基因组复制的调控	9	<0.01
BP	GO:1903900	病毒生命周期的调控	10	<0.01
BP	GO:0043903	共生的调节,包括通过寄生的互惠共生	11	<0.01
BP	GO:0019079	病毒基因组复制	9	<0.01
BP	GO:0045087	先天性免疫应答	17	<0.01
BP	GO:0050792	病毒变化的过程调节	10	<0.01
CC	GO:0005737	细胞质	26	<0.01
CC	GO:0034774	分泌颗粒内腔	4	<0.01
CC	GO:0005739	线粒体	8	<0.01
CC	GO:0060205	胞质囊腔	4	<0.01
CC	GO:0031983	囊腔	4	<0.01
CC	GO:0005741	线粒体外膜	3	<0.01
CC	GO:0062023	含胶原的细胞外基质	4	<0.01
CC	GO:0005775	空泡内腔	3	<0.01
CC	GO:0097232	层状体膜	1	<0.01
CC	GO:0097233	肺泡板层体膜	1	<0.01
CC	GO:0031968	细胞器外膜	3	<0.01
CC	GO:0019867	外膜	3	<0.01
CC	GO:0005637	核内膜	2	<0.01
CC	GO:0031966	线粒体膜	5	<0.01
CC	GO:0044444	胞质部分	22	<0.01
CC	GO:0005740	线粒体被膜	5	<0.01
CC	GO:0097013	吞噬泡腔	1	<0.01
MF	GO:0001730	2'-5'-寡聚腺苷酸合成酶活性	3	<0.01
MF	GO:0003725	双链RNA结合物	4	<0.01
MF	GO:0070566	腺苷转移酶活性	3	<0.01
MF	GO:0030550	乙酰胆碱受体抑制剂活性	2	<0.01
MF	GO:0005521	核纤层蛋白结合	2	<0.01
MF	GO:0030548	乙酰胆碱受体调节活性	2	<0.01
MF	GO:0099602	神经递质受体调节活性	2	<0.01
MF	GO:0016779	核苷酸转移酶活性	3	<0.01
MF	GO:0031700	肾上腺髓质受体结合	1	<0.01
MF	GO:0097655	丝氨酸蛋白酶抑制剂家族蛋白结合	1	<0.01

类别	项目	GO名称	基因数量	P值
BP	GO:0060337	Ⅰ型干扰素通路	14	<0.01
BP	GO:0071357	Ⅰ型干扰素的细胞反应	14	<0.01
BP	GO:0034340	Ⅰ型干扰素的应答	14	<0.01
BP	GO:0051607	对病毒的防御	14	<0.01
BP	GO:0009615	对病毒的应答	15	<0.01
BP	GO:0006952	防御反应	22	<0.01
BP	GO:0051707	对其他生物的反应	18	<0.01
BP	GO:0043207	对外界生物刺激的反应	18	<0.01
BP	GO:0009607	生物刺激反应	18	<0.01
BP	GO:0098542	对其他生物的防御反应	15	<0.01
BP	GO:0006955	免疫反应	23	<0.01
BP	GO:0045069	病毒基因组复制的调控	9	<0.01
BP	GO:1903900	病毒生命周期的调控	10	<0.01
BP	GO:0043903	共生的调节,包括通过寄生的互惠共生	11	<0.01
BP	GO:0019079	病毒基因组复制	9	<0.01
BP	GO:0045087	先天性免疫应答	17	<0.01
BP	GO:0050792	病毒变化的过程调节	10	<0.01
CC	GO:0005737	细胞质	26	<0.01
CC	GO:0034774	分泌颗粒内腔	4	<0.01
CC	GO:0005739	线粒体	8	<0.01
CC	GO:0060205	胞质囊腔	4	<0.01
CC	GO:0031983	囊腔	4	<0.01
CC	GO:0005741	线粒体外膜	3	<0.01
CC	GO:0062023	含胶原的细胞外基质	4	<0.01
CC	GO:0005775	空泡内腔	3	<0.01
CC	GO:0097232	层状体膜	1	<0.01
CC	GO:0097233	肺泡板层体膜	1	<0.01
CC	GO:0031968	细胞器外膜	3	<0.01
CC	GO:0019867	外膜	3	<0.01
CC	GO:0005637	核内膜	2	<0.01
CC	GO:0031966	线粒体膜	5	<0.01
CC	GO:0044444	胞质部分	22	<0.01
CC	GO:0005740	线粒体被膜	5	<0.01
CC	GO:0097013	吞噬泡腔	1	<0.01
MF	GO:0001730	2'-5'-寡聚腺苷酸合成酶活性	3	<0.01
MF	GO:0003725	双链RNA结合物	4	<0.01
MF	GO:0070566	腺苷转移酶活性	3	<0.01
MF	GO:0030550	乙酰胆碱受体抑制剂活性	2	<0.01
MF	GO:0005521	核纤层蛋白结合	2	<0.01
MF	GO:0030548	乙酰胆碱受体调节活性	2	<0.01
MF	GO:0099602	神经递质受体调节活性	2	<0.01
MF	GO:0016779	核苷酸转移酶活性	3	<0.01
MF	GO:0031700	肾上腺髓质受体结合	1	<0.01
MF	GO:0097655	丝氨酸蛋白酶抑制剂家族蛋白结合	1	<0.01

类型	名称	数量	描述	基因名称	FDR	P值
KEGG	hsa05164	5	甲型流感	RSAD2, OAS1, OAS2, OAS3, MX1	0.003173	<0.01
KEGG	hsa05162	4	麻疹	OAS1, OAS2, OAS3, MX1	0.012997	<0.01
KEGG	hsa05168	4	单纯疱疹病毒感染	SP100, OAS1, OAS2, OAS3	0.021615	<0.01
KEGG	hsa05160	3	丙型肝炎	OAS1, OAS2, OAS3	0.102459	0.02

类型	名称	数量	描述	基因名称	FDR	P值
KEGG	hsa05164	5	甲型流感	RSAD2, OAS1, OAS2, OAS3, MX1	0.003173	<0.01
KEGG	hsa05162	4	麻疹	OAS1, OAS2, OAS3, MX1	0.012997	<0.01
KEGG	hsa05168	4	单纯疱疹病毒感染	SP100, OAS1, OAS2, OAS3	0.021615	<0.01
KEGG	hsa05160	3	丙型肝炎	OAS1, OAS2, OAS3	0.102459	0.02