Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis
Summary: COVID-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 per...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220307185 |
| _version_ | 1818272990410833920 |
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| author | Nilesh Kumar Bharat Mishra Adeel Mehmood Mohammad Athar M Shahid Mukhtar |
| author_facet | Nilesh Kumar Bharat Mishra Adeel Mehmood Mohammad Athar M Shahid Mukhtar |
| author_sort | Nilesh Kumar |
| collection | DOAJ |
| description | Summary: COVID-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. |
| first_indexed | 2024-12-12T21:50:51Z |
| format | Article |
| id | doaj.art-af23dea9f0a14a0a937bd13c06257eab |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T21:50:51Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-af23dea9f0a14a0a937bd13c06257eab2022-12-22T00:10:47ZengElsevieriScience2589-00422020-09-01239101526Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 PathogenesisNilesh Kumar0Bharat Mishra1Adeel Mehmood2 Mohammad Athar3 M Shahid Mukhtar4Department of Biology, University of Alabama at Birmingham, 464 Campbell Hall, 1300 University Boulevard, AL 35294, USADepartment of Biology, University of Alabama at Birmingham, 464 Campbell Hall, 1300 University Boulevard, AL 35294, USADepartment of Biology, University of Alabama at Birmingham, 464 Campbell Hall, 1300 University Boulevard, AL 35294, USA; Department of Computer Science, University of Alabama at Birmingham, 1402 10th Avenue S., Birmingham, AL 35294, USADepartment of Dermatology, School of Medicine, University of Alabama at Birmingham, 1720 University Boulevard, AL 35294, USA; Corresponding authorDepartment of Biology, University of Alabama at Birmingham, 464 Campbell Hall, 1300 University Boulevard, AL 35294, USA; Nutrition Obesity Research Center, University of Alabama at Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA; Department of Surgery, University of Alabama at Birmingham, 1808 7th Avenue S, Birmingham, AL 35294, USA; Corresponding authorSummary: COVID-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.http://www.sciencedirect.com/science/article/pii/S2589004220307185VirologyOmics |
| spellingShingle | Nilesh Kumar Bharat Mishra Adeel Mehmood Mohammad Athar M Shahid Mukhtar Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis iScience Virology Omics |
| title | Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis |
| title_full | Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis |
| title_fullStr | Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis |
| title_full_unstemmed | Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis |
| title_short | Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis |
| title_sort | integrative network biology framework elucidates molecular mechanisms of sars cov 2 pathogenesis |
| topic | Virology Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220307185 |
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