Figure 2

The workflow of cooperative module identification and correlated genes identification. The input of the process is the weighted physical interaction (WPI) constructed in the first step of our methodology (Figure 1A). Steps 1, 2, and 3 of the process are used to identify cooperative module pairs. In step 1, a WPI network is constructed. Nodes of the WPI network represent genes and links represent direct physical interactions between gene products. The weight of each node represents the degree of necessity of that gene in the cell cycle. In step 2, the consistency score (CT_score) of each gene pair is calculated. Gene pairs with CT_score above the 99^th percentile are selected as seeds. In step 3, each seed is extended to a module pair. The spanning algorithm is used to search a pair of sub-networks in the WPI network that contain the seed and maximize the module' cooperation score (MCoop_score). The step 6, 7, and 8 of the process are used to identify correlated genes of each cooperative module pair. In step 7, for each identified module pair and each gene G in the WPI network, the significance of the number of physical interactions between G and genes contained in the module pair in the WPI network is evaluated by random network (see Additional file 1 for more details). For each identified module pair, genes that are significant associated with both modules are selected in step 8.