In network models of the interactome, these truncating mutations can be thought of as the removal of one node along with all its edges - a node removal. Nonconservative missense mutations of amino acids in the protein core that lead to major folding problems, protein aggregation, and premature protein degradation can also be modeled as node removals. At the other end of the mutational spectrum are small in-frame indels or missense mutations. These can preserve protein folding, but may modify the active site of an enzyme or affect the binding to another protein or macromolecule. In network models, these mutations, which specifically perturb a single molecular interaction, have been labeled as edge-specific or "edgetic". While investigation of the precise interaction defects associated with point mutations is of course not new, the term edgetic promotes a subtle yet meaningful archetype shift from conventional gene-centered models, which emphasize consideration of which specific edges are affected by a mutation, complement and extend classic gene-centric models, which ascertain only whether a gene product is present or not present and neglect less overt alterations of a given gene or gene product.

Joseph Loscalzo