Identifying dynamic network modules with temporal and spatial constraints

Despite the rapid accumulation of systems-level biological data, understanding the dynamic nature of cellular activity remains a difficult task. The reason is that most biological data are static, or only correspond to snapshots of cellular activity. In this study, we explicitly attempt to detangle the temporal complexity of biological networks by using compilations of time-series gene expression profiling data. We define a dynamic network module to be a set of proteins satisfying two conditions: (1) they form a connected component in the protein-protein interaction (PPI) network; and (2) their expression profiles form certain structures in the temporal domain. We develop an efficient mining algorithm to discover dynamic modules in a temporal network. Using yeast as a model system, we demonstrate that the majority of the identified dynamic modules are functionally homogeneous. Additionally, many of them provide insight into the sequential ordering of molecular events in cellular systems. Finally, we note that the applicability of our algorithm is not limited to the study of PPI networks, instead it is generally applicable to the combination of any type of network and time-series data.