Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load
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Abstract
SARS-CoV-2 is a betacoronavirus responsible for COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load without selective pressure and across the genome, compared to nsp7, nsp8 and nsp12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates and nsp14 mutations as potential predictors for high mutability strains.
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SciScore for 10.1101/2020.08.12.248732: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Genome sequence filtering, retrieval, and preprocessing: As previously described (Eskier et al., 2020), isolate genomes obtained from the GISAID EpiCoV database (date of accession: 17 June, 2020) were filtered to remove low-coverage or incomplete genomes, aligned against the reference genomic sequence for SARS-CoV-2, and processed to identify any SNVs present in the isolates and their impact on peptide sequences, if any, using the MAFFT, snp-sites, bcftools, and ANNOVAR suite of … SciScore for 10.1101/2020.08.12.248732: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Genome sequence filtering, retrieval, and preprocessing: As previously described (Eskier et al., 2020), isolate genomes obtained from the GISAID EpiCoV database (date of accession: 17 June, 2020) were filtered to remove low-coverage or incomplete genomes, aligned against the reference genomic sequence for SARS-CoV-2, and processed to identify any SNVs present in the isolates and their impact on peptide sequences, if any, using the MAFFT, snp-sites, bcftools, and ANNOVAR suite of software. MAFFTsuggested: (MAFFT, RRID:SCR_011811)ANNOVARsuggested: (ANNOVAR, RRID:SCR_012821)All statistical analyses were performed using IBM SPSS version 25.0 (Chicago, IL, USA). SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: Thank you for sharing your 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.
- 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.
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