Global modeling of transcriptional responses in interaction networks

Motivation: Cell-biological processes are regulated through a complex network of interactions between genes and their products. The processes, their activating conditions, and the associated transcriptional responses are often unknown. Organism-wide modeling of network activation can reveal unique and shared mechanisms between physiological conditions, and potentially as yet unknown processes. We introduce a novel approach for organism-wide discovery and analysis of transcriptional responses in interaction networks. The method searches for local, connected regions in a network that exhibit coordinated transcriptional response in a subset of conditions. Known interactions between genes are used to limit the search space and to guide the analysis. Validation on a human pathway network reveals physiologically coherent responses, functional relatedness between physiological conditions, and coordinated, context-specific regulation of the genes. Availability: Implementation is freely available in R and Matlab at http://netpro.r-forge.r-project.org