Overview of the methodology developed in this study. (A) Construction of the weighted physical interaction network (WPI network). The WPI network was established from protein-protein interaction (PPI) data, cell cycle expression data, and genome-wide location (ChIP-chip) data. Each node of the network indicates a gene, and each link indicates an interaction between two genes according to protein-protein interaction data and ChIP-chip data. The weight of each node was estimated by the correlations of gene pairs. We first established a co-expression network of nodes corresponding to genes and links corresponding to gene pairs with a Pearson correlation above 0.683 or below -0.683, and then we used the degree of each node in the network as its weight. (B) Identification of cooperative module pairs and correlated genes in each pair. Significantly cooperative module pairs were identified in the WPI network by a spanning algorithm. For each cooperative module pair, genes significantly correlated with both modules were also reported. (C) Cooperative module network and phase-related cooperation analyses. In this step, we evaluated our results and analyzed the structure and properties of the network generated by the cooperative module pairs, their interactions through correlated phase-regulated genes, and crosstalk mediated by phase-specific regulators. In addition, functionally cooperative module pairs and relationships in each phase of the cell cycle were inferred.