Dynamic gene network reconstruction from gene expression data in mice after influenza A (H1N1) infection

Konstantina Dimitrakopoulou,Klaus Schughart,Esther Wilk,Charalampos Tsimpouris,Kyriakos N Sgarbas,Anastasios Bezerianos,George Papadopoulos,Claudia Pommerenke

doi:10.1186/2043-9113-1-27

Abstract

BackgroundThe immune response to viral infection is a temporal process, represented by a dynamic and complex network of gene and protein interactions. Here, we present a reverse engineering strategy aimed at capturing the temporal evolution of the underlying Gene Regulatory Networks (GRN). The proposed approach will be an enabling step towards comprehending the dynamic behavior of gene regulation circuitry and mapping the network structure transitions in response to pathogen stimuli.ResultsWe applied the Time Varying Dynamic Bayesian Network (TV-DBN) method for reconstructing the gene regulatory interactions based on time series gene expression data for the mouse C57BL/6J inbred strain after infection with influenza A H1N1 (PR8) virus. Initially, 3500 differentially expressed genes were clustered with the use of k-means algorithm. Next, the successive in time GRNs were built over the expression profiles of cluster centroids. Finally, the identified GRNs were examined with several topological metrics and available protein-protein and protein-DNA interaction data, transcription factor and KEGG pathway data.ConclusionsOur results elucidate the potential of TV-DBN approach in providing valuable insights into the temporal rewiring of the lung transcriptome in response to H1N1 virus.

Highlights

The immune response to viral infection is a temporal process, represented by a dynamic and complex network of gene and protein interactions
The current study proposes a systems biology approach to analyze the dynamic behavior of the lung transcriptome to H1N1 infection from stimulus-response data from perturbation experiments
We present an implementation of Time Varying Dynamic Bayesian Networks on time series gene expression data of murine C57BL/6J inbred strain after infection with H1N1 (PR8) virus

Summary

Introduction

The immune response to viral infection is a temporal process, represented by a dynamic and complex network of gene and protein interactions. Moving forward, Bayesian networks (BN) utilize probability calculus and graph theory and model GRNs as directed acyclic graphs where the nodes represent genes and the edges between nodes represent regulatory interactions, based on the conditional dependencies extracted from the data. Despite their ability to deal with noisy input, they ignore the temporal dynamic aspects that characterize GRN modeling [7]. Linear additive regulation models managed to identify certain linear relations in regulatory systems but failed to attribute the nonlinear dynamics features [10]

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