T-CoV: a comprehensive portal of HLA-peptide interactions affected by SARS-CoV-2 mutations

  1. Stepan Nersisyan
  2. Anton Zhiyanov
  3. Maxim Shkurnikov
  4. Alexander Tonevitsky

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Abstract

Rapidly appearing SARS-CoV-2 mutations can affect T cell epitopes, which can help the virus to evade either CD8 or CD4 T-cell responses. We developed T-cell COVID-19 Atlas (T-CoV, https://t-cov.hse.ru) – the comprehensive web portal, which allows one to analyze how SARS-CoV-2 mutations alter the presentation of viral peptides by HLA molecules. The data are presented for common virus variants and the most frequent HLA class I and class II alleles. Binding affinities of HLA molecules and viral peptides were assessed with accurate in silico methods. The obtained results highlight the importance of taking HLA alleles diversity into account: mutation-mediated alterations in HLA-peptide interactions were highly dependent on HLA alleles. For example, we found that the essential number of peptides tightly bound to HLA-B*07:02 in the reference Wuhan variant ceased to be tight binders for the Indian (Delta) and the UK (Alpha) variants. In summary, we believe that T-CoV will help researchers and clinicians to predict the susceptibility of individuals with different HLA genotypes to infection with variants of SARS-CoV-2 and/or forecast its severity.

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  1. Version published to 10.1093/nar/gkab701
  2. ScreenIT

    SciScore for 10.1101/2021.07.06.451227: (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
    First, we constructed pairwise global alignment of the reference and mutated proteins using Biopython (16).
    Biopython
    suggested: (Biopython, RRID:SCR_007173)
    Aiming to compose a list of the most frequent HLA alleles, we first used CIWD v3.0.0 database (17).
    CIWD
    suggested: None
    The set of the most frequent HLA-DPA1 and HLA-DQA1 alleles was obtained from the PyPop database (18).
    PyPop
    suggested: (PYPOP, RRID:SCR_013425)
    Flask Python framework was used to build the website.
    Python
    suggested: (IPython, RRID:SCR_001658)
    Data processing and visualization were conducted with the extensive use of Pandas (19), NumPy (20), SciPy (21) and Seaborn (22)
    NumPy
    suggested: (NumPy, RRID:SCR_008633)
    SciPy
    suggested: (SciPy, RRID:SCR_008058)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We note several limitations of our work. The main limitation is since successful peptide presentation by HLA molecule does not guarantee further recognition by a TCR. Thus, clinical implications of significant alterations in HLA-peptide binding affinity should be further experimentally assessed. The second limitation involves officially unannotated SARS-CoV-2 proteins which could contain T cell epitopes: proteomics analysis carried out by Weingarten-Gabbay with co-authors resulted in detection of highly affine HLA-I peptides from out-of-frame ORFs (25). While some of these ORFs were included in our analysis (e.g., ORF9b), the other entries like S.iORF1/2 were not considered. Moreover, synonymous nucleotide substitutions which were ignored in our study could result in nonsynonymous amino acid substitutions in noncanonical reading frames. Such kind of analysis will be included in the next versions of T-CoV portal.

    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.

    About SciScore

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  3. Version published to 10.1101/2021.07.06.451227v1 on bioRxiv