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Open Access Highly Accessed Research article

Gene regulatory network modeling via global optimization of high-order dynamic Bayesian network

Nguyen Xuan1*, Madhu Chetty1*, Ross Coppel2 and Pramod P Wangikar3

Author Affiliations

1 Gippsland School of Information Technology, Monash University, Melbourne, Australia

2 Department of Microbiology, Monash University, Melbourne, Australia

3 Chemical Engineering Department, Indian Institute of Technology, Bombay, India

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BMC Bioinformatics 2012, 13:131  doi:10.1186/1471-2105-13-131

Published: 13 June 2012

Abstract

Background

Dynamic Bayesian network (DBN) is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN). Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks.

Results

To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT). GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques.

Conclusions

Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.