Accurately Detecting Protein Complexes by Graph Embedding and Combining Functions with Interactions.

Abstract

Identifying protein complexes is helpful for understanding cellular functions and designing drugs. In the last decades, many computational methods have been proposed based on detecting dense subgraphs or subnetworks in Protein-Protein Interaction Networks (PINs). However, the high rate of false positive/negative interactions in PINs prevents from the achievement of satisfactory detection results directly from PINs, because most of such existing methods exploit mainly topological information to do network partitioning. In this paper, we propose a new approach for protein complex detection by merging topological information of PINs and functional information of proteins. We first split proteins to a number of protein groups from the perspective of protein functions by using FunCat data. Then, for each of the resulting protein groups, we calculate two protein-protein similarity matrices: one is computed by using graph embedding over a PIN, the other is by using GO terms, and combine these two matrices to get an integrated similarity matrix. Following that, we cluster the proteins in each group based on the corresponding integrated similarity matrix, and obtain a number of small protein clusters. We map these clusters of proteins onto the PIN, and get a number of connected subgraphs. After a round of merging of overlapping subgraphs, finally we get the detected complexes. We conduct empirical evaluation on four PPI datasets (Collins, Gavin, Krogan, and Wiphi) with two complex benchmarks (CYC2008 and MIPS). Experimental results show that our method performs better than the state-of-the-art methods.