Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions

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Abstract

Understanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.

The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploiting the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.

Extensive analysis performed to understand the network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins, mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.

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  1. SciScore for 10.1101/2020.07.29.226217: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    (KEGG) database 1 for the genes involved in those pathways [28].
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    We use SciPy version 1.5.0 4 for computing ρ.
    SciPy
    suggested: (SciPy, RRID:SCR_008058)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. SciScore for 10.1101/2020.07.29.226217: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We use SciPy version 1.5.0 4 for computing ρ.
    SciPy
    suggested: (SciPy, RRID:SCR_008058)
    We use BioGRID [49] to calculate the centrality score of our candidate host proteins 6 .
    BioGRID
    suggested: (BioGrid Australia, RRID:SCR_006334)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  3. SciScore for 10.1101/2020.07.29.226217: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We use SciPy version 1.5.0 (sipy
    SciPy
    suggested: (SciPy, RRID:SCR_008058)
    We use BioGRID [49] to calculate the centrality score of our candidate host proteins 6 .
    BioGRID
    suggested: (BioGrid Australia, RRID:SCR_006334)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. SciScore for 10.1101/2020.07.29.226217: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We use SciPy version 1.5.0 4 for computing ρ.
    SciPy
    suggested: (SciPy, RRID:SCR_008058)
    We use BioGRID [49] to calculate the centrality score of our candidate host proteins 6 .
    BioGRID
    suggested: (BioGrid Australia, RRID:SCR_006334)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  5. SciScore for 10.1101/2020.07.29.226217: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    To collect significant host genes involved in our candidate 17 signaling pathways, we search Kyoto Encyclopedia of Genes and Genomes (KEGG) Table 1:
    KEGG
    suggested: (KEGG, SCR_012773)
    We use SciPy version 1.5.0 4 for computing ρ.
    SciPy
    suggested: (SciPy, SCR_008058)
    We use BioGRID [49] to calculate the centrality score of our candidate host proteins 6 .
    BioGRID
    suggested: (BioGrid Australia, SCR_006334)

    Data from additional tools added to each annotation on a weekly basis.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.