Decomposing PPI networks for complex discovery

Abstract

Protein complexes are important for understanding principles of cellular organization and functions. With the availability of large amounts of high-throughput proteinprotein interactions (PPI), many algorithms have been proposed to discover protein complexes from PPI networks. However, none of existing algorithms takes into consideration the fact that not all the interactions in a PPI network take place at the same time. As a result, predicted complexes often contain many spuriously included proteins, precluding them from matching true complexes. We propose two methods to tackle this problem: (1) We utilize cellular component Gene Ontology (GO) terms to decompose PPI networks into several smaller networks such that the proteins in each decomposed network are annotated with the same cellular component GO term. (2) Hub proteins are more likely to fuse clusters that correspond to different complexes. To avoid this, we remove hub proteins from PPI networks, and then apply a complex discovery algorithm on the remaining PPI network. The removed hub proteins are added back to the generated clusters afterwards. We tested the two methods on the yeast PPI network downloaded from BioGRID. Our results show that these methods can improve the performance of several complex discovery algorithms significantly. Further improvement in performance is achieved when we apply them in tandem.