Co-regulated Protein Functional Modules with Varying Activities in Dynamic PPI Networks

Current methods for the detection of differential gene expression focus on finding individual genes that may be responsible for certain diseases or external irritants. However, for common genetic diseases, multiple genes and their interactions should be understood and treated together during the exploration of disease causes and possible drug design. The present study focuses on analyzing the dynamic patterns of co-regulated modules during biological progression and determining those having remarkably varying activities, using the yeast cell cycle as a case study. We first constructed dynamic active protein-protein interaction networks by modeling the activity of proteins and assembling the dynamic co-regulation protein network at each time point. The dynamic active modules were detected using a method based on the Bayesian graphical model and then the modules with the most varied dispersion of clustering coefficients, which could be responsible for the dynamic mechanism of the cell cycle, were identified. Comparison of results from our functional module detection with the state-of-art functional module detection methods and validation of the ranking of activities of functional modules using GO annotations demonstrate the efficacy of our method for narrowing the scope of possible essential responding modules that could provide multiple targets for biologists to further experimentally validate.