Analysis of bioinformatics in pediatric influenza based on chip with high-throughput

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

Abstract

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

CLC Number:

R511.7

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

Add to citation manager EndNote|Ris|BibTeX

URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2021.09.010

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

Figures/Tables 11

References 19

[1]	Itolikar S, Nadkar MY. H1N1 revisited after six years: Then and now[J]. J Assoc Physicians India, 2015, 63:41-43. pmid: 26591169
[2]	Webster RG, Govorkova EA. Continuing challenges in influenza[J]. Ann N Y Acad Sci, 2014, 1323(1):115-39. doi: 10.1111/nyas.12462 URL
[3]	Kondrich J, Rosenthal M. Influenza in children[J]. Curr Opin Pediatr, 2017, 29(3):297-302. doi: 10.1097/MOP.0000000000000495 URL
[4]	Committee On Infectious Diseases. Recommendations for prevention and control of influenza in children, 2019-2020[J]. Pediatrics, 2019, 144(4):e20192478. doi: 10.1542/peds.2019-2478 URL
[5]	Shim JM, Kim J, Tenson T, et al. Influenza virus infection, interferon response, viral counter-response, and apoptosis[J]. Viruses, 2017, 9(8):223. doi: 10.3390/v9080223 URL
[6]	Hou F, Sun L, Zheng H, et al. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response[J]. Cell, 2011, 146(3):448-461. doi: 10.1016/j.cell.2011.06.041 URL
[7]	Yoshizumi T, Ichinohe T, Sasaki O, et al. Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity[J]. Nat Commun, 2014, 5:4713. doi: 10.1038/ncomms5713 pmid: 25140902
[8]	Wang R, Zhu Y, Lin X, et al. Influenza M2 protein regulates MAVS-mediated signaling pathway through interacting with MAVS and increasing ROS production[J]. Autophagy, 2019, 15(7):1163-1181. doi: 10.1080/15548627.2019.1580089 URL
[9]	Xu F, Song H, An B, et al. NF-κB-dependent IFIT3 induction by HBx promotes Hepatitis B virus replication[J]. Front Microbiol, 2019, 10:2382. doi: 10.3389/fmicb.2019.02382 URL
[10]	Yang Y, Zhou Y, Hou J, et al. Hepatic IFIT3 predicts interferon-α therapeutic response in patients of hepatocellular carcinoma[J]. Hepatology, 2017, 66(1):152-166. doi: 10.1002/hep.v66.1 URL
[11]	Li Y, Wen Z, Zhou H, et al. Porcine interferon-induced protein with tetratricopeptide repeats 3, poIFIT3, inhibits swine influenza virus replication and potentiates IFN-β production[J]. Dev Comp Immunol, 2015, 50(1):49-57. doi: 10.1016/j.dci.2014.10.008 URL
[12]	Lindenmann J. Resistance of mice to mouse-adapted influenza A virus[J]. Virology, 1962, 16:203-204. doi: 10.1016/0042-6822(62)90297-0 URL
[13]	Jung HE, Oh JE, Lee HK. Cell-penetrating Mx1 enhances anti-viral resistance against mucosal influenza viral infection[J]. Viruses, 2019, 11(2):109. doi: 10.3390/v11020109 URL
[14]	Lohöfener J, Steinke N, Kay-Fedorov P, et al. The activation mechanism of 2'-5'-oligoadenylate synthetase gives new insights into OAS/cGAS triggers of innate immunity[J]. Structure, 2015, 23(5):851-862. doi: S0969-2126(15)00090-8 pmid: 25892109
[15]	Li Y, Banerjee S, Wang Y, et al. Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses[J]. Proc Natl Acad Sci U S A, 2016, 113(8):2241-2246. doi: 10.1073/pnas.1519657113 URL
[16]	Sadler AJ, Williams BR. Interferon-inducible antiviral effectors[J]. Nat Rev Immunol, 2008, 8:559-568. doi: 10.1038/nri2314 URL
[17]	Mihm U, Ackermann O, Welsch C, et al. Clinical relevance of the 2'-5'-oligoadenylate synthetase/RNase L system for treatment response in chronic hepatitis C[J]. J Hepatol, 2009, 50:49-58. doi: 10.1016/j.jhep.2008.08.024 URL
[18]	Liao X, Xie H, Li S, et al. 2', 5'-oligoadenylate synthetase 2 (OAS2) inhibits Zika virus replication through activation of type Ⅰ IFN signaling pathway[J]. Viruses, 2020, 12(4):418. doi: 10.3390/v12040418 URL
[19]	Tang BM, Shojaei M, Parnell GP, et al. A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection[J]. Eur Respir J, 2017, 49(6):1602098. doi: 10.1183/13993003.02098-2016 URL

组别	基因
下调	SP100 IFI6 IFI44L LAMP3 SERPING1 OAS2 PLSCR1 RNASE2 NEXN CTSL IFI27 IFI35 OAS3 RSAD2 OAS1 MX1 MPO LY6E LGALS3BP ADM XAF1 SPATS2L EPSTI1 OASL HIST2H2BE IFI44 H1F0 ISG15 IFIT3
上调	FCER1A

组别	基因
下调	SP100 IFI6 IFI44L LAMP3 SERPING1 OAS2 PLSCR1 RNASE2 NEXN CTSL IFI27 IFI35 OAS3 RSAD2 OAS1 MX1 MPO LY6E LGALS3BP ADM XAF1 SPATS2L EPSTI1 OASL HIST2H2BE IFI44 H1F0 ISG15 IFIT3
上调	FCER1A

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