Extended Data Fig. 2: Sequence features explain the readthrough variability across PTCs and drugs.

a–i, Effect of the sequence feature (x-axis) on readthrough efficiency (y-axis) colored by drug. The top and bottom sides of the box are the lower and upper quartiles. The box covers the interquartile interval, where 50% of the data are found. The horizontal line that splits the box in two is the median. Only variants where the stop codon is UGA are shown (except for c and e, where all stop codon variants are shown). The sequence features are the three nucleotides downstream of the PTC (n = 10645, p < 2e−16, Kruskal–Wallis test) (a), the three nucleotides upstream of the PTC (n = 10645, p < 2e−16) (b), the stop type (n = 22227, p < 2e−16) (c), the nucleotide in position +1 downstream of the PTC (n = 10502, p < 2e−16) (d), same as d but stratified by stop codon (n = 16753) (e), the amino acid upstream of the PTC (n = 10602, p < 2e−16) (f), variants with a glutamic acid upstream of the PTC stratified by the codon (n = 613) (g), variants with an arginine upstream of the PTC stratified by the codon (n = 1040, p = 3e−6) (h), and the effect of amino acids encoded by A-ending codons on readthrough efficiency for FUr, gentamicin, CC90009 and SJ6986, where codons ended in A display higher readthrough efficiencies compared to the rest of the codons (n = 7902, adjusted p < 1e−3, one-sided Wilcoxon signed-rank test). The nucleotide in position +3 of the codon is denoted with colors (i). j, Mean readthrough difference between pairs of codons with Hamming distance of 1 (that is, single nucleotide difference) that encode for the same amino acid, or pairs that encode a different amino acid across drugs. P value of the two-sided t-test between the same amino acid and different amino acid groups is shown. k,l, Readthrough distributions (k) and pairwise correlations (l) for the three SJ6986 concentrations tested (0.5 μM, 5 μM and 20 μM).

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