Prediction and analysis of human-herpes simplex virus type 1 protein-protein interactions by integrating multiple method
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RESEARCH ARTICLE Prediction and analysis of human-herpes simplex virus type 1 protein-protein interactions by integrating multiple methods Xianyi Lian1, Xiaodi Yang1, Jiqi Shao2, Fujun Hou3, Shiping Yang4,*, Dongli Pan3, Ziding Zhang1,* 1
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China 2 National Demonstration Center for Experimental Biological Sciences Education, College of Biological Sciences, China Agricultural University, Beijing 100193, China 3 Department of Medical Microbiology and Parasitology, and Department of Infectious Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China 4 State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100193, China * Correspondence: [email protected], [email protected] Received May 2, 2020; Revised July 3, 2020; Accepted July 27, 2020 Background: Herpes simplex virus type 1 (HSV-1) is a ubiquitous infectious pathogen that widely affects human health. To decipher the complicated human-HSV-1 interactions, a comprehensive protein-protein interaction (PPI) network between human and HSV-1 is highly demanded. Methods: To complement the experimental identification of human-HSV-1 PPIs, an integrative strategy to predict proteome-wide PPIs between human and HSV-1 was developed. For each human-HSV-1 protein pair, four popular PPI inference methods, including interolog mapping, the domain-domain interaction-based method, the domainmotif interaction-based method, and the machine learning-based method, were optimally implemented to generate four interaction probability scores, which were further integrated into a final probability score. Results: As a result, a comprehensive high-confidence PPI network between human and HSV-1 was established, covering 10,432 interactions between 4,546 human proteins and 72 HSV-1 proteins. Functional and network analyses of the HSV-1 targeting proteins in the context of human interactome can recapitulate the known knowledge regarding the HSV-1 replication cycle, supporting the overall reliability of the predicted PPI network. Considering that HSV-1 infections are implicated in encephalitis and neurodegenerative diseases, we focused on exploring the biological significance of the brain-specific human-HSV-1 PPIs. In particular, the predicted interactions between HSV-1 proteins and Alzheimer’s-disease-related proteins were intensively investigated. Conclusion: The current work can provide testable hypotheses to assist in the mechanistic understanding of the human-HSV-1 relationship and the anti-HSV-1 pharmaceutical target discovery. To make the predicted PPI network and the datasets freely accessible to the scientific community, a user-friendly database browser was released at http:// www.zzdlab.com/HintHSV/index.php.
Keywords: human-virus interaction; protein-protein interaction; prediction; herpes simplex virus type 1; Alzheimer’s disease
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