The bootstrapping procedure for calculating the 95% confidence interval of median CADD38 PHRED max codon scores and further characterizing the differences between low, medium, and highly reactive residues was performed as follows: original CADD38 max scores for each sub‐group were resampled 20,000 times with replacement, with the median of each bootstrapped sample calculated. This process produced 20,000 samples with 895 low, 412 medium, and 94 high observations for CpD Cys, and 3,401 low, 660 medium, and 302 high observations for CpD Lys.

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