Human leukocyte antigen susceptibility map for SARS-CoV-2

Austin Nguyen; Julianne K David; Sean K Maden; Mary A Wood; Benjamin R Weeder; Abhinav Nellore; Reid F Thompson

kmerized each of these sequences into 8-to 12-mers to assess MHC class I-peptide binding affinity across the entire proteome. MHC class I binding affinity predictions were performed using 145 different HLA alleles for which global allele frequency data was available as described previously (72) (see Supplementary Table S1 S5) with netMHCpan v4.0 (73) using the '-BA' option to include binding affinity predictions and the '-l' option to specify peptides of lengths 8-12 (Supplementary Table S1 ). Binding affinity was not predicted for peptides containing the character '|' in their sequences. Additional MHC class I binding affinity predictions were performed on all 66 MHCflurry supported alleles (--list-supported-alleles, Supplementary Figures S7-S10 ). We further cross-referenced these lists of peptides with existing experimentally validated SARS-CoV epitopes present in the Immune Epitope Database (Supplementary Table S4 ) (76) . We then performed consensus binding affinity predictions for the 66 supported alleles shared by all three tools by taking the union set of alleles and filtering for peptide-allele pairs matching the union set of alleles. 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. In all cases, we used the netchop v3.0 (77) "C-term" model with a cleavage threshold of 0.1 to further remove any peptides that were not predicted to undergo canonical MHC class I antigen processing via proteasomal cleavage (of the peptide's C-terminus).