Integrated Bioinformatics Analysis Identifies Hub Genes Associated with Viral Infection and Alzheimer’s Disease

Article type: Research Article

Authors: Sun, Xiaoru^{a; b; c; 1} | Zhang, Hui^{d; 1} | Yao, Dongdong^{e; f} | Xu, Yaru^d | Jing, Qi^d | Cao, Silu^d | Tian, Li^{a; b; c; *} | Li, Cheng^{a; b; c; *}

Affiliations: [a] Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, P.R. China | [b] Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, P.R. China | [c] Clinical Research Center for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, P.R. China | [d] Department of Anesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, P.R. China | [e] Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Anesthesiology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Li Tian and Cheng Li, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China. Tel.: +86 15301705322; E-mails: [email protected] (LT); [email protected] (CL).

Note: [1] These authors contributed equally to this work.

Abstract: Background: Alzheimer’s disease (AD) is a fatal neurodegenerative disease, the etiology of which is unclear. Previous studies have suggested that some viruses are neurotropic and associated with AD. Objective: By using bioinformatics analysis, we investigated the potential association between viral infection and AD. Methods: A total of 5,066 differentially expressed genes (DEGs) in the temporal cortex between AD and control samples were identified. These DEGs were then examined via weighted gene co-expression network analysis (WGCNA) and clustered into modules of genes with similar expression patterns. Of identified modules, module turquoise had the highest correlation with AD. The module turquoise was further characterized using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. Results: Our results showed that the KEGG pathways of the module turquoise were mainly associated with viral infection signaling, specifically Herpes simplex virus, Human papillomavirus, and Epstein-Barr virus infections. A total of 126 genes were enriched in viral infection signaling pathways. In addition, based on values of module membership and gene significance, a total of 508 genes within the module were selected for further analysis. By intersecting these 508 genes with those 126 genes enriched in viral infection pathways, we identified 4 hub genes that were associated with both viral infection and AD: TLR2, COL1A2, NOTCH3, and ZNF132. Conclusion: Through bioinformatics analysis, we demonstrated a potential link between viral infection and AD. These findings may provide a platform to further our understanding of AD pathogenesis.

Keywords: Alzheimer’s disease, anti-viral, bioinformatics analysis, hub genes, viral infection

DOI: 10.3233/JAD-215232

Journal: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1053-1061, 2022