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Open Access Highly Accessed Methodology article

A computational framework for gene regulatory network inference that combines multiple methods and datasets

Rita Gupta1, Anna Stincone1, Philipp Antczak1, Sarah Durant2, Roy Bicknell2, Andreas Bikfalvi3 and Francesco Falciani1*

Author Affiliations

1 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

2 Institute of Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

3 INSERM E 0113, Molecular Angiogenesis Laboratory, Université de Bordeaux 1, 33405 Talence, France

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BMC Systems Biology 2011, 5:52  doi:10.1186/1752-0509-5-52

Published: 13 April 2011

Abstract

Background

Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective.

Results

This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies.

Conclusions

The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.