Genetic alteration of human MYH6 is mimicked by SARS-CoV-2 polyprotein: mapping viral variants of cardiac interest

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1. Version published to 10.1038/s41420-022-00914-9

   Mar 21, 2022
2. 

   ScreenIT

   Dec 1, 2021

   SciScore for 10.1101/2021.11.23.469709: (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
   Sentences	Resources
   For single cell RNA-seq studies, processed count matrices were accessed from Gene Expression Omnibus or other publicly available data repositories.	Gene Expression Omnibus suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
   Each dataset was processed using Scrublet and Seurat v3.0 as described previously.18,41–43 Cell type annotations were obtained from associated metadata files if available; otherwise, annotation was performed manually, guided by the cell types reported in the associated publication.	Seurat suggested: (SEURAT, RRID:SCR_007322)
   Similarly, we used a sliding window …

   SciScore for 10.1101/2021.11.23.469709: (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
   Sentences	Resources
   For single cell RNA-seq studies, processed count matrices were accessed from Gene Expression Omnibus or other publicly available data repositories.	Gene Expression Omnibus suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)
   Each dataset was processed using Scrublet and Seurat v3.0 as described previously.18,41–43 Cell type annotations were obtained from associated metadata files if available; otherwise, annotation was performed manually, guided by the cell types reported in the associated publication.	Seurat suggested: (SEURAT, RRID:SCR_007322)
   Similarly, we used a sliding window approach to generate all 8-mers from the reference amino acid sequences of the previously defined 144 cardiac proteins, including the canonical isoforms and all described isoforms indicated in UniProt.	UniProt suggested: (UniProtKB, RRID:SCR_004426)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   There are a few limitations to this study. First, the human proteins that we surveyed were shortlisted based on their overexpression in cardiac tissue. There could be mimicked proteins that are shared between cardiac tissues and other tissues that are not accounted for in the current analysis. Second, there are other mechanisms that could contribute to autoimmunity after viral infection such as bystander activation, epitope spreading, and viral persistence34. Third, the presence of identical peptides in cardiac proteins and the SARS-CoV-2 proteome could occur due to chance. Comparing all SARS-CoV-2 8-mers to a set of brain enriched proteins and a set of skin enriched proteins shows a similar probability distribution of Hamming distance (Supplementary Figure S2), suggesting that the observed similarity with SARS-CoV-2 peptides is not specific to human cardiac proteins. Fourth, it is possible that peptides with lower degrees of similarity could contribute to immunologic mimicry, as T cells can be highly cross reactive against different major histocompatibility complex (MHC)-presented peptides.35–39 Taken together, by studying the intersection of human genetic variation in cardiac proteins and SARS-CoV-2 evolution, we have identified candidates of molecular mimicry that have potential to contribute to cardiac inflammation in the context of COVID-19. It will be important to perform follow-up functional studies evaluating the potential of SARS-CoV-2 reactive T cells and antibodies...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

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

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   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.

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

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3. 

   Version published to 10.1101/2021.11.23.469709v1 on bioRxiv

   Nov 29, 2021