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

Retrieval of SARS-CoV-2 sequence 13 The GenBank reference sequence for SARS-CoV-2 (accession: NC_045512.2) was used for this 14 study. All twelve annotated open-reading frames (orf1a, orf1b, S, ORF3a, E, M, ORF6, ORF7a, 15 ORF7b, ORF8, N, and ORF10) were considered as sources of potential epitopes. The copyright holder for this preprint (which was not peer-reviewed) is the .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 B alleles, and 18 HLA-C alleles. Peptide-allele pairs were assigned a percent rank by comparing 1 their binding scores to those of 1,000,000 reference peptides for the same respective allele. Peptide-allele pairs that scored in the top 1% of the scores of these reference peptides were 3 considered strong potential binders. 4 These top-ranking peptides were then prioritized based on expected USA population coverage 5 (allele frequencies obtained from (32) -USA frequencies calculated as follows: The cumulative product itself represents the chance that an individual in the USA does not 14 express any one of the contained alleles; hence, the complement describes the probability that at 15 least one is present. The aim of using USA, European, and API allele frequencies is to cover a 16 diverse population where allele frequency estimates are relatively reliable. 17 We then construct two ranked lists of HLA-I epitopes by coverage. The first ranks the epitopes 18 by their absolute coverage, such that sequences predicted to bind similar collections of alleles 19 would be ranked similarly (Supplementary Table 4 ). The second list, referred to as the "disjoint" 20 list, is constructed in an iterative fashion where the sequence with the greatest coverage is 21 selected first, and then the coverage for the remaining epitopes is updated to nullify contributions 22 author/funder. All rights reserved. No reuse allowed without permission.