Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets

  1. Agnes P. Chan
  2. Yongwook Choi
  3. Nicholas J. Schork

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Abstract

The CoV disease 2019 (COVID-19) infectious disease outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths.

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  1. Version published to 10.1128/msphere.00754-20
  2. ScreenIT

    SciScore for 10.1101/2020.07.06.190207: (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
    Coronavirus family sequence conservation analysis: The SARS-CoV-2 NCBI RefSeq genome (NC_045512.2) was used as the reference.
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    , processed peptides, and UTRs) of SARS-CoV-2 was searched against the 109 representative CoV genomes collected from four genera (alpha, beta, gamma, and delta) (Table S1) using NCBI BLAST+
    NCBI
    suggested: (NCBI, RRID:SCR_006472)
    The maximum likelihood phylogeny tree was constructed using RAxML (v8.2.11) with 100 bootstraps under the GTRGAMMA model (48).
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    An MSA was performed on the collected 693 genome sequences including SARS-CoV-2 reference genome using Clustal Omega (v1.2.4).
    Clustal Omega
    suggested: (Clustal Omega, RRID:SCR_001591)
    In addition, an MSA of the 18,599 genomes was built using MAFFT (v6.861b), which was used for independent validations of major mutation positions (51).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    The functional impact of amino acid substitutions and indels were predicted using PROVEAN (26).
    PROVEAN
    suggested: (PROVEAN, RRID:SCR_002182)
    Linkage disequilibrium (LD) analysis was performed to identify co-evolving variants among SNVs with frequency of 0.1% or higher using Tagger implemented in Haploview (v4.2) (52).
    Haploview
    suggested: (Haploview, RRID:SCR_003076)
    Identification of putatively interacting human microRNAs: The UTR sequences of SARS-CoV-2 and SARS-CoV were used to search against the miRBase mature RNA sequences (Release 22.1) (31) using blastn with the following parameters set for short sequences: “-penalty −4 -reward 5 -gapopen 25 -gapextend 10 -dust no -soft_masking false.” For cross-species conservation analysis in other organisms, we searched the miRBase database requiring 18 or more bases matched with 100% sequence identity.
    blastn
    suggested: (BLASTN, RRID:SCR_001598)
    miRBase
    suggested: (miRBase, RRID:SCR_017497)
    A SARS-CoV-2 gene-by-gene BLAST analysis was performed against the CoV family genomes at nucleotide and amino acid sequence levels.
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.07.06.190207v1 on bioRxiv