Bioinformatics analysis of genes differentially expressed in autism and screening of hub genes in the occurrence and development of autism
Journal of Translational Neuroscience. 2022, 7 (1): 15-22.
Objective: to screen the genes differentially expressed in autism using bioinformatics methods, and to explore their functional enrichment, related signaling pathways and the tissue-specific expression of hub genes. Methods: the autism expression profile chip numbered GSE77103 in the Gene Expression Omnibus (GEO) database was selected for examination. R language and related R packages were used for the screening and visualization of the differentially expressed genes. Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis of the differential genes were carried out using the relevant R package of R language. The database STRING was used to construct the interaction network of the proteins encoded by the differentially expressed genes, and the software Cytoscape was used to screen the hub genes in the network. The selected hub genes were imported into the BioGPS database to analyze the tissue-specific expression of the hub genes. Results: six hundred and sixty differentially expressed genes were screened out. Three hundred and seventy-three up-regulated genes and 287 down-regulated genes in the peripheral blood mononuclear cells of autistic children were compared with the peripheral blood mononuclear cells of healthy children. GO functional enrichment results showed that biological processes (BP) were mainly involved in viral response, negative regulation of viral genome replication, negative regulation of multiple biological processes, negative regulation of viral life cycle, and defense responses to viruses. Cell components (CC) were involved in vesicles, lysosomal membranes, lysosomal lumen, etc.; molecular functions (MF) were involved in regulating glutathione transferase activity, peroxidase activity, oxidoreductase activity, Glutathione peroxidase and transferase activity, etc. The results of KEGG signaling pathway analysis showed that the differentially expressed genes were related to the lysosomal pathway, the glutathione metabolism pathway and the arachidonic acid metabolism pathway. The hub genes screened by cytoHubba were: interferon regulatory factor 7 (IRF7), interferon stimulated exonuclease gene 15 (ISG15), XIAP associated factor 1 (XAF1), MX dynamin like GTPase 1 (MX1), interferon induced protein with tetratricopeptide repeats 1 (IFIT1), interferon induced protein with tetratricopeptide repeats 5 (IFIT5), 2’-5’-oligoadenylate synthetase 3 (OAS3), interferon induced protein 44 (IFI44), HECT and the RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), interferon stimulated exonuclease gene 20 (ISG20). Conclusion: there are genes that are differentially expressed in the peripheral blood mononuclear cells of autistic toddlers and healthy toddlers. IRF7, ISG15, XAF1, MX1, IFIT1, IFIT5, OAS3, IFI44, HERC5, ISG20 are the hub regulatory genes of autism.
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