From networks of protein interactions to networks of functional dependencies

Reasoning that topological features (e.g., clusters of highly inter-connected proteins) might help approaching structured and non-redundant understanding of molecular function, an algorithm was developed that prioritizes inclusion of proteins into the function nodes that best overlap protein clusters. Specifically, the algorithm identifies function nodes (and their mutual relations), based on the topological analysis of a protein interaction network, which can be related to various biological domains, such as cellular components (e.g., peroxisome and cellular bud) or biological processes (e.g., cell budding) of the model organism S. cerevisiae.The method we have described allows converting a protein interaction network into a non-redundant process graph of inter-dependent function nodes. The examples we have described show that the resulting graph allows researchers to formulate testable hypotheses about dependencies among functions and the underlying mechanisms.In recent years, small- and large-scale experiments have produced a considerable wealth of information about the physical interactions of thousands of molecules. Proteins, in particular, have been reported to interact physically with other proteins, as well as with genes, transcripts and metabolites. Various types of protein-protein interactions (PPI) have been documented, ranging from PPI that bring about assembly of stable protein complexes to PPI that cause transient modifications (e.g., phosphorylation) of target proteins. Retrieving PPI from available databases enables system-level analysis of protein interactomes in various model organisms. Furthermore, suitable tools are available for representing the interactomes, including the PPI networks, which display proteins and PPI as nodes and edges, respectively [1].In addition to the interactions, also the functions of numerous proteins have been characterized broadly. Evidence about protein function can be retrieved (among other sources) from the vocabular