Global modeling of transcriptional responses in interaction networks

TL;DR

This paper presents a new method for analyzing organism-wide transcriptional responses within gene interaction networks, identifying coordinated responses and revealing shared mechanisms across conditions.

Contribution

A novel approach that uses known gene interactions to discover and analyze localized, coordinated transcriptional responses across the entire organism.

Findings

Revealed physiologically coherent responses in human pathway networks.

Identified functional relatedness between different physiological conditions.

Showed coordinated, context-specific gene regulation.

Abstract

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