文章基本信息

标题：Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis
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作者：Nilesh Kumar ; Bharat Mishra ; Adeel Mehmood 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：9
页码：1-32
DOI：10.1016/j.isci.2020.101526
语种：English
出版社：Elsevier
摘要：SummaryCOVID-19 (coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the pathophysiology of this virus is complex and largely unknown, we employed a network-biology-fueled approach and integrated transcriptome data pertaining to lung epithelial cells with human interactome to generate Calu-3-specific human-SARS-CoV-2 interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 targets central nodes of the host-viral network, which participate in core functional pathways. Network centrality analyses discover 33 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation, and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host-modifying responses and cytokine storm. Overall, our network-centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into the pathogenicity of SARS-CoV-2 that may help foster effective therapeutic design.Graphical AbstractDisplay OmittedHighlights•A network-biology-fueled approach to integrate multiomics data of host-viral network•Network centrality and pathway enrichment analyses reveal 33 high-value targets•Dynamic regulatory circuitry and molecular events pertinent to COVID-19•Underlying molecular mechanisms and pathways of SARS-CoV-2 pathogenesisVirology; Omics