Extended Data Fig. 3. Antibody escapability from deep mutational scanning measurements and in natural SARS-CoV-2 mutants.

a, To calculate antibody escapability (Fig. 1b,c), mutation escape fractions were weighted by their deleterious consequences for ACE2 binding or RBD expression. Top plots show the weighting factor (y-axis) for mutation effects on ACE2 binding (left) and RBD expression (right). This weight factor was multiplied by the mutation escape fraction in the summation to calculate antibody escapability as described in the Methods. Histograms show the distribution of mutation effects on ACE2 binding (left) and RBD expression (right) for all mutations that pass our computational filtering steps (bottom), and mutations that are found with at least 20 sequence counts on GISAID (middle). b, Correlation in antibody relative epitope size (top) and escapability (bottom) calculated from independent deep mutational scanning replicates, compared to the averaged replicates shown in Fig. 1b,c. R², squared Pearson correlation coefficient. c, Scatterplots illustrate the degree to which a mutation escapes antibody binding (escape fraction, y-axis) and its frequency among 1,190,241 high-quality human-derived SARS-CoV-2 sequences present on GISAID as of May 2, 2021. Large escape mutations (>5x global median escape fraction) for each antibody with non-zero mutant frequencies are labeled. Plot labels report the sum of mutant frequencies for all labeled mutations, corresponding to the natural SARS-CoV-2 mutant escape frequency for antibodies shown in Fig. 4d,g.