Investigating the human host - ssRNA virus interaction landscape using the SMEAGOL toolbox

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Abstract

Viruses are intracellular parasites that need their host cell to reproduce. Consequently, they have evolved numerous mechanisms to exploit the molecular machinery of their host cells, including the broad spectrum of host RNA-binding proteins (RBPs). However, the RBP interactome of viral genomes and the consequences of these interactions for infection are still to be mapped for most RNA viruses. To facilitate these efforts we have developed SMEAGOL, a fast and user-friendly toolbox to analyze the enrichment or depletion of RBP binding motifs across RNA sequences ( https://github.com/gruber-sciencelab/SMEAGOL ). To shed light on the interaction landscape of RNA viruses with human host cell RBPs at a large scale, we applied SMEAGOL to 197 single-stranded RNA (ssRNA) viral genome sequences. We find that the majority of ssRNA virus genomes are significantly enriched or depleted in binding motifs for human RBPs, suggesting selection pressure on these interactions. Our analysis provides an overview of potential virus - RBP interactions, covering the majority of ssRNA viral genomes fully sequenced to date, and represents a rich resource for studying host interactions vital to the virulence of ssRNA viruses. Our resource and the SMEAGOL toolbox will support future studies of virus / host interactions, ultimately feeding into better treatments.

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  1. SciScore for 10.1101/2021.12.02.470930: (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
    Curation of viral genomes: The complete genome sequences for viruses (Taxonomy ID: 10239) deposited in the NCBI repository (https://www.ncbi.nlm.nih.gov/genome/browse#!/viruses/) were retrieved using the following search / filter strategies: only RefSeq entries of specific families of (+)ssRNA and (-)ssRNA viruses known to infect humans (host = “human”) were selected (Table 1).
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    We manually curated these data by adding missing information from additional viral databases ViPR (https://www.viprbrc.org) 65 and ViralZone (https://viralzone.expasy.org/) 66.
    ViralZone
    suggested: (ViralZone, RRID:SCR_006563)
    PWMs from ENCODE RNA Bind-n-Seqassays 8 were constructed using the ENCODE computational pipeline 8 and added to this list.
    ENCODE
    suggested: (Encode, RRID:SCR_015482)
    Variant Effect Prediction: We downloaded information on 36,688 SARS-CoV-2 mutations from the GESS database (https://wan-bioinfo.shinyapps.io/GESS/) on September 14, 2021.
    Variant Effect Prediction
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.


    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.

    Results from scite Reference Check: We found no unreliable references.


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