Interactomics emerged from biophysics in the early ‘90s, after high-throughput qualitative assays, such as pulldown, yeast 2-hybrid, or phage-display, became widely available. Its main questions are “what are the interactions that occur between molecules of our cells”, however, this is a fundamentally qualitative perspective, constrained by the tools used in the field. From a biophysical point of view, interactions can be studied by either asking “how strong is their intrinsic binding affinity“ or “how much complex is expected to form under certain cellular conditions“ between these intrinsic and extrinsic properties, one can define mathematical functions.
To overcome the technical limitations of qualitative interactomics, our group develop innovative techniques that can experimentally measure affinity interactomes proteome-wide of either minimal binding fragments or full-length proteins. Using these, we can now investigate intrinsic affinity-interactomes and combine them with state-of-the-art proteomics via rule-based modeling to estimate amounts of formed complexes for cellular states. The resulting complexomes can provide a functional layer between descriptive biology (such as proteomics) and observed phenotypes revealing new dimensions of cellular signaling and its malfunctions under disease. I will present our latest methods through simple examples and show how it is possible to exploit affinity interactomes and predicted complexomes to decipher complex cellular mechanisms
Published on November 7, 2022