PEPPER: cytoscape app for protein complex expansion using protein-protein interaction networks

We introduce PEPPER (Protein complex Expansion using Protein-protein intERactions), a Cytoscape app designed to identify protein complexes as densely connected subnetworks from seed lists of proteins derived from proteomic studies. PEPPER identifies connected subgraph by using multi-objective optimization involving two functions: (i) the coverage, a solution must contain as many proteins from the seed as possible, (ii) the density, the proteins of a solution must be as connected as possible, using only interactions from a proteome-wide interaction network. Comparisons based on gold standard yeast and human datasets showed Pepper's integrative approach as superior to standard protein complex discovery methods. The visualization and interpretation of the results are facilitated by an automated post-processing pipeline based on topological analysis and data integration about the predicted complex proteins. PEPPER is a user-friendly tool that can be used to analyse any list of proteins.