Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

Asaf Poran; Dewi Harjanto; Matthew Malloy; Michael S. Rooney; Lakshmi Srinivasan; Richard B. Gaynor

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.06.027805 doi: bioRxiv preprint HLA-II alleles for viral pathogen epitopes. We used all assays of Coronaviridae family viruses 1 with human hosts from ViPR as our validation dataset. Assays that did not have an associated four-2 digit HLA allele or were associated with an allele our models did not support were omitted (see 3 Supplementary Tables 1 and 2 for a list of supported alleles). 4 For HLA-I, within the validation dataset there were a total of 4,445 unique peptide-HLA allele 5 pairs that were assayed for MHC-binding, using variations of: 1) cellular MHC or purified MHC; 6 2) a direct or competitive assay; and 3) measured by fluorescence or radioactivity. Two additional 7 peptide-MHC allele pairs were confirmed via X-ray crystallography. Depending on the study from 8 which the data was collected, peptide-MHC allele pairs were either binarily defined in ViPR as 9 "Negative" and "Positive" for binding, or with a more granular scale of positivity: Low, 10 Intermediate, and High. We assigned peptide-MHC allele pairs with multiple measurements with 11 the highest MHC-binding detected across the replicates (see Methods). 12 We then applied our HLA-I binding predictor from RECON to the peptide-MHC allele pairs in 13 the validation dataset and compared the computed HLA-I percent ranks of these pairs with the 14 reported MHC-binding assay results (Supplementary Table 8) . A low percent rank value 15 corresponds to high likelihood of binding (e.g., a peptide with a percent rank of 1% scores amongst 16 the top 1% of the reference peptides). The percent ranks of peptide-MHC allele pairs that had a 17 binary "Positive" result in the MHC-binding assay were significantly lower than pairs with a 18 "Negative" result. Further, in the more granular positive results, stronger assay results (low < 19 intermediate < high) were associated with increasingly lower percent ranks ( Figure 1A) . In 20 addition, the two peptide-MHC alleles that were confirmed by X-ray crystallography were 21 predicted as very likely binders, with low percent rank scores of 0.07% and 0.30%. These results 22 author/funder. All rights reserved. No reuse allowed without permission.