Protein Complexes Identification with Family-Wise Error Rate Control

The detection of protein complexes from protein-protein interaction network is a fundamental issue in bioinformatics and systems biology. To solve this problem, numerous methods have been proposed from different angles in the past decades. However, the study on detecting statistically significant protein complexes still has not received much attention. Although there are a few methods available in the literature for identifying statistically significant protein complexes, none of these methods can provide a more strict control on the error rate of a protein complex in terms of family-wise error rate (FWER). In this paper, we propose a new detection method SSF that is capable of controlling the FWER of each reported protein complex. More precisely, we first present a p-value calculation method based on Fisher's exact test to quantify the association between each protein and a given candidate protein complex. Consequently, we describe the key modules of the SSF algorithm: a seed expansion procedure for significant protein complexes search and a set cover strategy for redundancy elimination. The experimental results on five benchmark data sets show that: (1) our method can achieve the highest precision; (2) it outperforms three competing methods in terms of normalized mutual information (NMI) and F1 score in most cases.