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Identification of COVID-19-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets

Chen Su, View ORCID ProfileSimon Rousseau, Amin Emad
doi: https://doi.org/10.1101/2020.12.23.424177
Chen Su
1Department of Electrical and Computer Engineering, McGill University, Montréal, QC, Canada
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Simon Rousseau
2The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute, & Department of Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada
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  • For correspondence: amin.emad@mcgill.ca simon.rousseau@mcgill.ca
Amin Emad
1Department of Electrical and Computer Engineering, McGill University, Montréal, QC, Canada
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  • For correspondence: amin.emad@mcgill.ca simon.rousseau@mcgill.ca
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ABSTRACT

Identification of transcriptional regulatory mechanisms and signaling networks involved in the response of host to infection by SARS-CoV-2 is a powerful approach that provides a systems biology view of gene expression programs involved in COVID-19 and may enable identification of novel therapeutic targets and strategies to mitigate the impact of this disease. In this study, we combined a series of recently developed computational tools to identify transcriptional regulatory networks involved in the response of epithelial cells to infection by SARS-CoV-2, and particularly regulatory mechanisms that are specific to this virus. In addition, using network-guided analyses, we identified signaling pathways that are associated with these networks and kinases that may regulate them. The results identified classical antiviral response pathways including Interferon response factors (IRFs), interferons (IFNs), and JAK-STAT signaling as key elements upregulated by SARS-CoV-2 in comparison to mock-treated cells. In addition, comparing SARS-Cov-2 infection of airway epithelial cells to other respiratory viruses identified pathways associated with regulation of inflammation (MAPK14) and immunity (BTK, MBX) that may contribute to exacerbate organ damage linked with complications of COVID-19. The regulatory networks identified herein reflect a combination of experimentally validated hits and novel pathways supporting the computational pipeline to quickly narrow down promising avenue of investigations when facing an emerging and novel disease such as COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 23, 2020.
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Identification of COVID-19-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets
Chen Su, Simon Rousseau, Amin Emad
bioRxiv 2020.12.23.424177; doi: https://doi.org/10.1101/2020.12.23.424177
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Identification of COVID-19-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets
Chen Su, Simon Rousseau, Amin Emad
bioRxiv 2020.12.23.424177; doi: https://doi.org/10.1101/2020.12.23.424177

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