Stability of Metabolic Correlations under Changing Environmental Conditions in Escherichia coli – A Systems Approach

Background: Biological systems adapt to changing environments by reorganizing their cellular 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 underlying 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 condition-dependent 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 observations about the changes of metabolic concentrations. The approach was tested with Escherichia coli as a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diauxie) 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 pathways, and (3) independently of the response scale, based on their importance in the reorganization of the correlation 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-based approach does not rely on major changes in concentration to identify metabolites important for stress 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

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Unravelling the role of epigenetics in reproductive adaptations to early-life environment

Reproductive function adjusts in response to environmental conditions in order to optimize success. In humans, this plasticity includes age of pubertal onset, hormone levels and age at menopause. These reproductive characteristics vary across populations with distinct lifestyles and following specific childhood events, and point to a role for the early-life environment in shaping adult reproductive trajectories. Epigenetic mechanisms respond to external signals, exert long-term effects on gene expression and have been shown in animal and cellular studies to regulate normal reproductive function, strongly implicating their role in these adaptations. Moreover, human cohort data have revealed differential DNA methylation signatures in proxy tissues that are associated with reproductive phenotypic variation, although the cause–effect relationships are difficult to discern, calling for additional complementary approaches to establish functionality. In this Review, we summarize how adult reproductive function can be shaped by childhood events. We discuss why the influence of the childhood environment on adult reproductive function is an important consideration in understanding how reproduction is regulated and necessitates consideration by clinicians treating women with diverse life histories. The resolution of the molecular mechanisms responsible for human reproductive plasticity could also lead to new approaches for intervention by targeting these epigenetic modifications