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Open Access Highly Accessed Methodology article

Inference of dynamical gene-regulatory networks based on time-resolved multi-stimuli multi-experiment data applying NetGenerator V2.0

Michael Weber1, Sebastian G Henkel2*, Sebastian Vlaic1, Reinhard Guthke1, Everardus J van Zoelen3 and Dominik Driesch2

Author Affiliations

1 , Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Beutenbergstr. 11a, 07745 Jena, Germany

2 , BioControl Jena GmbH, Wildenbruchstr. 15, 07745 Jena, Germany, www.biocontrol-jena.com

3 Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen, The Netherlands

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BMC Systems Biology 2013, 7:1  doi:10.1186/1752-0509-7-1

Published: 2 January 2013

Abstract

Background

Inference of gene-regulatory networks (GRNs) is important for understanding behaviour and potential treatment of biological systems. Knowledge about GRNs gained from transcriptome analysis can be increased by multiple experiments and/or multiple stimuli. Since GRNs are complex and dynamical, appropriate methods and algorithms are needed for constructing models describing these dynamics. Algorithms based on heuristic approaches reduce the effort in parameter identification and computation time.

Results

The NetGenerator V2.0 algorithm, a heuristic for network inference, is proposed and described. It automatically generates a system of differential equations modelling structure and dynamics of the network based on time-resolved gene expression data. In contrast to a previous version, the inference considers multi-stimuli multi-experiment data and contains different methods for integrating prior knowledge. The resulting significant changes in the algorithmic procedures are explained in detail. NetGenerator is applied to relevant benchmark examples evaluating the inference for data from experiments with different stimuli. Also, the underlying GRN of chondrogenic differentiation, a real-world multi-stimulus problem, is inferred and analysed.

Conclusions

NetGenerator is able to determine the structure and parameters of GRNs and their dynamics. The new features of the algorithm extend the range of possible experimental set-ups, results and biological interpretations. Based upon benchmarks, the algorithm provides good results in terms of specificity, sensitivity, efficiency and model fit.

Keywords:
Gene-regulatory networks; Network inference; Heuristic algorithm; ODE; NetGenerator