Fig. 3: Prepandemic EVEscape is as accurate as intrapandemic experimental scans at anticipating pandemic variation.
From: Learning from prepandemic data to forecast viral escape
a, Percentages of top decile predicted escape mutations by EVEscape, mutational scan experiments (Bloom Set, Supplementary Table 5) and a previous computational model42 seen more than 100 times in GISAID by each date since the start of the pandemic. EVEscape using prepandemic sequences anticipates pandemic variation at least on par with mutational scan experiments using antibodies and sera available 10 or 17 months into the pandemic. Analysis focuses only on non-synonymous point mutations that are a single nucleotide distance away from the Wuhan viral sequence, as well as on the RBD of Spike as that is where experimental data are available. b, Percentages of observed pandemic mutations in top decile of escape predictions by observed frequency during the pandemic. High-frequency mutations in particular are well-captured by EVEscape. c, Most of the RBD mutations observed in VOC strains have high EVEscape scores and lower scores in the mutational scan experiments against pandemic sera. This is true even when considering a further set of mutations identified in mutational scanning experiments as significantly improving (in the top 2%) either RBD expression or ACE2 binding. d, EVEscape can predict escape mutations in the epitope of the former therapeutic antibody bamlanivimab. E484 is involved in a salt bridge with R96 and R50 of bamlanivimab, which lost Food and Drug Administration emergency use authorization owing to the emergence of Omicron, wherein E484A or E484K mutations (both predicted in the top 1% of EVEscape Spike predictions) escape binding because of the loss of these salt bridges41.e, Precision-recall curve for RBD escape predictions of EVEscape, EVEscape fitness component only (EVE model) and a previous computational model42 compared with DMS escape mutations (AUPRC reported with a comparison with a ‘null’ model in which escape mutations are randomly predicted). expr, expression.; no., number.
