Fig. 2
Assessing the impact of disruptive alleles on protein function. a Fraction of protein pairs recovered by PCA for disrupted and intact interactions in comparison to positive and random reference sets (PRS and RRS). P values by one-tailed Z-test between disrupted and intact interactions. P values by two-tailed Z-test for all other comparisons. b Fraction of disruptive variants in ExAC (blue) across four allele frequency ranges (i) <0.1%, (ii) 0.1 – 1.0%, (iii) 1.0 – 10%, and (iv) >100%. P value by chi-square test. Fraction of disruptive somatic mutations in COSMIC (purple) in known cancer-affiliated genes or other genes and fraction of disruptive germline disease-associated genes from HGMD (red) are also shown. P values by one-tailed Z-test. c Reported number of functional missense variants per individual genome varies extensively across different studies. d ExAC variants tested against ≥ 2 interactions further partitioned into three disruption categories. Distribution of e allele frequency, f Grantham scores, and g PolyPhen-2 scores across three disruption categories. Error bars in a and b indicate + SE of proportion. Thick black bars in g are the interquartile range, white dots display the median, and extended thin black lines represent 95% confidence intervals. P values in e, and g by one-tailed U-test. P values in f by two-tailed U-test. See also Supplementary Tables 1–3, Supplementary Data 2–4, and Supplementary Fig. 1
