Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2
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Abstract
Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.
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SciScore for 10.1101/2020.03.22.20040600: (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 each protein class (i.e. ORF1ab, S, M, E, N), all 34 coronavirus sequences were aligned using the Clustal Omega Clustal Omegasuggested: (Clustal Omega, RRID:SCR_001591)Conserved peptide assessment: Aligned sequences were imported into Jalview v. Jalviewsuggested: (Jalview, RRID:SCR_006459)Peptide-MHC class I binding affinity predictions: FASTA-formatted input protein sequences from the entire SARS-CoV-2 and SARS-CoV proteomes were obtained from NCBI RefSeq database (67) under accession numbers NC_045512.2 and NC_004718.3. RefSeqsuggested: (RefSeq, RRID:SCR_003496)For the SARS-CoV and … SciScore for 10.1101/2020.03.22.20040600: (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 each protein class (i.e. ORF1ab, S, M, E, N), all 34 coronavirus sequences were aligned using the Clustal Omega Clustal Omegasuggested: (Clustal Omega, RRID:SCR_001591)Conserved peptide assessment: Aligned sequences were imported into Jalview v. Jalviewsuggested: (Jalview, RRID:SCR_006459)Peptide-MHC class I binding affinity predictions: FASTA-formatted input protein sequences from the entire SARS-CoV-2 and SARS-CoV proteomes were obtained from NCBI RefSeq database (67) under accession numbers NC_045512.2 and NC_004718.3. RefSeqsuggested: (RefSeq, RRID:SCR_003496)For the SARS-CoV and SARS-CoV-2 specific distribution of per-allele proteome presentation, we exclude all peptides-allele pairs with >500nM predicted binding. SARS-CoV-2suggested: (Active Motif Cat# 91351, RRID:AB_2847848)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We note, however, several limitations to this our work. First and foremost, while we note that a handful of our binding affinity predictions were borne out in experimentally validated SARS-CoV peptides (Supplementary Table S4), we acknowledge that this is an entirely in silico study. As we are unable to obtain individual-level HLA typing and clinical outcomes data for any real-world COVID-19 populations at this time, the data presented is theoretical in nature, and subject to many of the same limitations implicit to the MHC binding affinity prediction tool(s) upon which it is based. As such, we are unable to assess the relative importance of HLA type compared to known disease-modifying risk factors such as age and clinical comorbidities (5–10). We further note that peptide-MHC binding affinity is limited as a predictor of subsequent T-cell responses (54–56), and we do not study T-cell responses herein. As such, we are ill-equipped to explore phenomena such as original antigenic sin (57–59), where prior exposure to closely related infection(s) may trigger T-cell anergy (60–62) or immunopathogenesis (63) in the setting of a novel infection. We explored only a limited set of 145 well-studied HLA alleles, but note that this analysis could be performed across a wider diversity of genotypes (49). Additionally, we did not assess genotypic heterogeneity or in vivo evolution of SARS-CoV-2, which could modify the repertoire of viral epitopes presented, or otherwise modulate virulence i...
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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