Interactome Quotes

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

Despite the advancements of systematic experimental pipelines, literature-curated protein-interaction data continue to be the primary data for investigation of focused biological mechanisms. Notwithstanding the variable quality of curated interactions available in public databases, the impact of inspection bias on the ability of literature maps to provide insightful information remains equivocal. The problems posed by inspection bias extend beyond mapping of protein interactions to the development of pharmacological agents and other aspects of modern biomedicine. Essentially the same 10% of the proteome is being investigated today as was being investigated before the announcement of completion of the reference genome sequence. One way forward, at least with regard to interactome mapping, is to continue the transition toward systematic and relatively unbiased experimental interactome mapping. With continued advancement of systematic protein-interaction mapping efforts, the expectation is that interactome 'deserts', the zones of the interactome space where biomedical knowledge researchers simply do not look for interactions owing to the lack of prior knowledge, might eventually become more populated. Efforts at mapping protein interactions will continue to be instrumental for furthering biomedical research. ~ Joseph Loscalzo