Identifying function modules from protein–protein interaction networks based on Szemerédi’s Regularity Lemma

Abstract

Szemerédi’s Regularity Lemma (SRL) is a crucial tool in the analysis of large graphs, having made significant contributions in the proof of some sensational results in mathematics. Traditional methods for studying proteins in Protein–Protein Interaction (PPI) networks typically only extract the first-order or second-order neighbor information of proteins, ignoring the potential third-order or higher-order neighbor information between proteins, which may hide certain relationships between proteins. To explore more in-depth insights for PPI networks, we take into account the fourth-order neighbor information of proteins and reconstruct the network in this paper, naming it the weighted dense PPI network. We then partition it using SRL, which primarily utilizes the structural information and corresponds to a unique partition of the original network. Bioinformatics analyses such as those for pathway enrichment analysis and multiple sequence alignment show that our method can classify interacting protein pairs, grouping proteins with functional association, disease association, and sequence similarity together. Overall, this paper has three essential contributions: (1) we present a new model to overcome the astronomically large demand of vertices in applying SRL, and achieve protein classification; (2) we reconstruct a weighted dense PPI network which can make SRL work and mine potential interactions more efficiently; and (3) proteins in the same class partitioned by our method not only have sequence similarity, but also have functional associations.