Fig. 1.

The overall design of My Personal Mutanome. The human interactome is a network of protein-protein interactions where proteins are the nodes and interactions are the edges. Perturbations, such as those originated from mutations, alter the networks by either directly affecting the nodes (nodetic) or affecting the edges (edgetic). Nodetic mutations are those that can affect the function of a protein, such as post-translational modification and ligand-binding. For example, the phosphorylation sites of catenin beta-1 (encoded by CTNNB1) (I) are affected by the mutations at the same sites or in close vicinity. The ligand-binding site of KRAS (III) can also be affected by the nodetic mutations. Edgetic mutations are those on the PPI interfaces that perturb the interaction. For example, several mutations on the PPI interface (red) of PIK3CA (IV) and PIK3R1 (V) perturb the interaction. Nodetic and edgetic network perturbations by mutations may promote tumorigenesis, results in altered patient survival and drug responses. By integrating the survival and drug responses and 3D structural information, MPM helps to identify actionable mutations and provides implication of the mechanisms at the human interactome level