Extended Data Fig. 3: Proteogenomics of the PIONEER-predicted interactome network.

a, Phosphorylation-associated PPI-perturbing mutations altered the proteomic changes in COAD and UCEC. The abundance of proteins was quantified using the TMT technique. Data are represented as a box plot with an underlaid violin plot in which the middle line is the median, the lower and upper edges of the box are the first and third quartiles, the whiskers represent IQR × 1.5, and the dots are outlier points. Significance was determined by two-tailed Wilcoxon rank-sum test. The n numbers are shown in Supplementary Table 17. b, Phosphorylation-associated PPI-perturbing mutations in the EGFR–RAS–RAF–MEK–ERK cascade signaling pathway. The whole transmembrane EGFR structures were constructed by three crystal structures (PDB: 3NJP, 2M20, 2GS6). The membrane model is shown in green. The phosphorylation sites are indicated by the symbol 'P'. The detailed interface structure of SOS1–KRAS is also shown in the inset. The key mutated residue Gln61 on KRAS forms a hydrogen bond (purple dashed line) with residue Thr935 on SOS1, and Tyr884 on SOS1 is involved in a cation-π interaction (red dash line) with residue Arg73 on KRAS. Two subunits of RAF protein structure models were built by RAF1 and BRAF, separately (PDB: 6VJJ and 6Q0J). The two subunits are connected by a disordered loop indicated by blue cartoon lines. Two heterodimers of KRAS–RAF1 and BRAF–MEK1 constitutes the KRAS–RAF–MEK1 complex. PDB ID of each complex structure model is provided. c, Highlighted examples of drug responses. Data are represented as a box plot with an underlaid violin plot in which the middle line is the median, the lower and upper edges of the box are the first and third quartiles, the whiskers represent IQR × 1.5, and the dots are outlier points. Significance was determined by ANOVA. The n numbers are shown in Supplementary Table 16.