Fig. 2: Analyses of mutations that impact phase separation (PS).
From: Decoding Missense Variants by Incorporating Phase Separation via Machine Learning
a Comparison of the PS propensity of proteins corresponding to collected mutations (70 proteins) with that of the human proteome. (PScore35, Left; PhaSePred-SaPS43, Right; ****P < 0.0001, two-sided Mann–Whitney U test, p = 4.6e-11 and 3.3e-14, respectively; the boxplot components within each violin, from top to bottom are maxima, upper quartile, median, lower quartile, and minima.). b The proportion of ‘Impact’ mutations (Left) located in IDRs and Domains, compared with the total proportion of IDRs and Domains (Right). c The top 30 high-frequency mutations among collected ‘Impact’ mutations. d Distribution of amino acid (AA) distances from each mutation site to the nearest domain boundary. Distances of ‘Impact’ mutations and random ‘Background’ positions were compared within Domains (Left) and within IDRs (Right) (The number of data points were 139, 1000, 202, and 1000, respectively; ****P < 0.0001, two-sided Mann–Whitney U test, p = 4.4e-40 and 1.4e-30, respectively; the boxplot components within each violin plot from top to bottom are maxima, upper quartile, median, lower quartile, and minima). e Distribution of eight pi-contact prediction values (PPVs) for mutation sites. Values of ‘Impact’ mutations (in red) and ‘Background’ mutations (in gray) were compared. The dot in each violin represents the average of values. (NS not significant, **P < 0.01, ****P < 0.0001, two-sample Kolmogorov–Smirnov test; P-values are 0.0029, 0.140, 5.9e-11, 1.2e-7, 0.106, 3.3e-8, 4.5e-6, and 4.1e-14, respectively). f Statistical comparison of the changes of AA property index before and after mutation between collected ‘Strengthen’ (n = 79, orange) and ‘Weaken/Disable’ groups (n = 228, blue) under two-sample Kolmogorov–Smirnov D test (WT wild-type AA, MT mutant AA). The direction of the D statistic was set as positive when the mean value of the ‘Strengthen’ group was higher and as negative when that of the ‘Weaken’ group was higher. Source data are provided as a Source Data file.
