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

Conserved peptide assessment Aligned sequences were imported into Jalview v. 2.1.1 (71) with automated generation of the following alignment annotations: 1) sequence consensus, calculated as the percentage of the modal residue per column, 2) sequence conservation (0-11), measured as a numerical index reflecting conservation of amino acid physico-chemical properties in the alignment, 3) alignment quality (0-1), measured as a normalized sum of BLOSUM62 ratios for all residues at each position, 4) occupancy, calculated as the number of aligned residues (not including gaps) for each position. In all cases, sequence conservation was assessed for each of three groups: only human coronaviruses (n=7), all betacoronaviruses (n=16), and combined alpha-and betacoronavirus sequences (n=34). Aligned SARS-CoV-2 sequence and all annotations were manually exported for subsequent analysis. Conserved human coronavirus peptides were defined as those with a length ≥8 consecutive amino acids, each with an agreement of SARS-CoV-2 and ≥4 other human coronavirus sequences with the consensus sequence (Supplementary Table S2 ). For each of these conserved peptides, we also assessed the component number of 8-to 12-mers sharing identical amino acid sequence between SARS-CoV-2 and each of the four other common human coronaviruses (i.e. OC43, HKU1, NL63, 229E) (Supplementary Table S3 ). For all peptides, human, beta, and combined conservation scores were obtained using a custom R v.3.6.2 script as the mean sequence conservation (minus gap penalties where relevant) (see https://github.com/pdxgx/covid19).