Stability of metabolic correlations under changing environmental conditions in Escherichia coli : a systems approach

  • Background: Biological systems adapt to changing environments by reorganizing their cellula r and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underl ying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic conditiondependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple ob servation s about the changes of metabolic concentrations. The approach was tested with Escherichia colias a model organism observed under four different environmental stress conditions (cold stress, Background: Biological systems adapt to changing environments by reorganizing their cellula r and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underl ying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic conditiondependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple ob servation s about the changes of metabolic concentrations. The approach was tested with Escherichia colias a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diau xie) and control unperturbed conditions. By constructing the stable network component, which displays a scale free topology and small-world characteristics, we demonstrated that: (1) metabolite hubs in this reconstructed correlation networks are significantly enriched for those contained in biochemical networks such as EcoCyc, (2) particular components of the stable network are enriched for functionally related biochemical path ways, and (3) ind ependently of the response scale, based on their importance in the reorganization of the cor relation network a set of metabolites can be identified which represent hypothetical candidates for adjusting to a stress-specific response. Conclusions/Significance: Network-based tools allowed the identification of stress-dependent and general metabolic correlation networks. This correlation-network-ba sed approach does not rely on major changes in concentration to identify metabolites important for st ress adaptation, but rather on the changes in network properties with respect to metabolites. This should represent a useful complementary technique in addition to more classical approaches.show moreshow less

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Metadaten
Author:Jedrzej Szymanski, Szymon Jozefczuk, Zoran Nikoloski, Joachim Selbig, Victoria Nikiforova, Gareth Catchpole, Lothar Willmitzer
URN:urn:nbn:de:kobv:517-opus-45253
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (paper 147)
Document Type:Postprint
Language:English
Date of Publication (online):2010/07/21
Year of Completion:2009
Publishing Institution:Universität Potsdam
Release Date:2010/07/21
Tag:Small-world networks; gene-expression; saccharomyces-cerevisiae; stress-response; trehalose synthesis
Source:PLoS one 4 (2009), 10, Art. e7441, DOI: 10.1371/journal.pone.0007441
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (English):License LogoCreative Commons - Attribution 3.0 unported
Notes extern:
The article was originally published by PUBLIC LIBRARY SCIENCE:
PLoS one. - 4 (2009), 10, Art. e7441 (15 S.)
ISSN 1932-6203
DOI 10.1371/journal.pone.0007441