Fig. 4. Developability parameter sensitivity can be quantified by analyzing mutated variants of wildtype antibodies.

a DP values were computed for all possible single amino acid substituted mutants of 500 sampled wildtype human V_H antibody sequences (100 sequences sampled per isotype; n = 301,777 independent mutants in total). Values of each DP were scaled and mean-centered. The sensitivity was quantified for each DP by analyzing the DP dispersion of the mutants from their corresponding wildtype. Average sensitivity was measured by excess kurtosis (small kurtosis = high average sensitivity), while potential sensitivity was measured by the range (see Methods). b Average and potential sensitivity of selected sequence-based DPs. c Average and potential sensitivity of DPs from (B) grouped by antibody region in which the mutation occurred. In both (b) and (c), numerical values on the x-axis represent the median of the corresponding sensitivity metric. Supplementary Figs. 11 and 12.