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Open Access Highly Accessed Methodology article

Using gene expression data and network topology to detect substantial pathways, clusters and switches during oxygen deprivation of Escherichia coli

Gunnar Schramm1, Marc Zapatka1, Roland Eils12* and Rainer König12

Author Affiliations

1 Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

2 Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, 69120 Heidelberg, Germany

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BMC Bioinformatics 2007, 8:149  doi:10.1186/1471-2105-8-149

Published: 8 May 2007

Abstract

Background

Biochemical investigations over the last decades have elucidated an increasingly complete image of the cellular metabolism. To derive a systems view for the regulation of the metabolism when cells adapt to environmental changes, whole genome gene expression profiles can be analysed. Moreover, utilising a network topology based on gene relationships may facilitate interpreting this vast amount of information, and extracting significant patterns within the networks.

Results

Interpreting expression levels as pixels with grey value intensities and network topology as relationships between pixels, allows for an image-like representation of cellular metabolism. While the topology of a regular image is a lattice grid, biological networks demonstrate scale-free architecture and thus advanced image processing methods such as wavelet transforms cannot directly be applied. In the study reported here, one-dimensional enzyme-enzyme pairs were tracked to reveal sub-graphs of a biological interaction network which showed significant adaptations to a changing environment. As a case study, the response of the hetero-fermentative bacterium E. coli to oxygen deprivation was investigated. With our novel method, we detected, as expected, an up-regulation in the pathways of hexose nutrients up-take and metabolism and formate fermentation. Furthermore, our approach revealed a down-regulation in iron processing as well as the up-regulation of the histidine biosynthesis pathway. The latter may reflect an adaptive response of E. coli against an increasingly acidic environment due to the excretion of acidic products during anaerobic growth in a batch culture.

Conclusion

Based on microarray expression profiling data of prokaryotic cells exposed to fundamental treatment changes, our novel technique proved to extract system changes for a rather broad spectrum of the biochemical network.