G-network modelling based abnormal pathway detection in gene regulatory networks

Abstract

Gene expression centered gene regulatory networks studies can provide insight into the dynamics of pathway activities that depend on changes in their environmental conditions. Thus we propose a new pathway analysis approach to detect differentially behaving pathways in abnormal conditions based on G-network theory. Using this approach gene regulatory network model parameters are estimated from normal and abnormal samples using optimization techniques with corresponding constraints. We show that in a "p53 network" application, the proposed method effectively detects anomalous activated/inactivated pathways related with MDM2, ATM/ATR and RB1 genes, which could not be observed from previous analyses of gene regulatory network normal and abnormal behaviour. © 2012 Springer-Verlag London Limited.