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

Schramm G, Zapatka M, Eils R, König R - BMC Bioinformatics (2007)

Bottom Line: 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.Furthermore, our approach revealed a down-regulation in iron processing as well as the up-regulation of the histidine biosynthesis pathway.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. g.schramm@dkfz.de <g.schramm@dkfz.de>

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.

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Metabolisms of hexose nutrients under anaerobic conditions. Fructose and mannose metabolism were up-regulated indicating a higher glucose processing. For box colours see Figure 4.
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Figure 5: Metabolisms of hexose nutrients under anaerobic conditions. Fructose and mannose metabolism were up-regulated indicating a higher glucose processing. For box colours see Figure 4.

Mentions: The metabolic network of E. coli underwent substantial changes in regulation, when adapting to the environmental change from oxygen rich to deprived conditions (Figure 1). Due to limited oxygen, glycolysis and the fructose/mannose metabolism was up-regulated securing energy production under anaerobic conditions (Figure 5). Furthermore, pyruvate metabolism, formate fermentation and mixed acid fermentation were also up-regulated fermenting the products of the glycolysis (Figure 4). In contrast, iron processing and oxidative stress responses were down-regulated as oxidative stress was reduced (Figure 6). As expected, the aerobic part of the TCA-cycle was down-regulated. The need to generate essential compounds and amino acids was indicated by an elevated level of the aspartate metabolism (Figure 7). An indirect effect of the oxygen rich to oxygen deprived conditions was the up-regulation of the histidine biosynthesis (Figure 7). Histidine may function as a buffer for produced acids accumulating in the batch culture. In the following, these findings are described in detail.


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

Schramm G, Zapatka M, Eils R, König R - BMC Bioinformatics (2007)

Metabolisms of hexose nutrients under anaerobic conditions. Fructose and mannose metabolism were up-regulated indicating a higher glucose processing. For box colours see Figure 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1884177&req=5

Figure 5: Metabolisms of hexose nutrients under anaerobic conditions. Fructose and mannose metabolism were up-regulated indicating a higher glucose processing. For box colours see Figure 4.
Mentions: The metabolic network of E. coli underwent substantial changes in regulation, when adapting to the environmental change from oxygen rich to deprived conditions (Figure 1). Due to limited oxygen, glycolysis and the fructose/mannose metabolism was up-regulated securing energy production under anaerobic conditions (Figure 5). Furthermore, pyruvate metabolism, formate fermentation and mixed acid fermentation were also up-regulated fermenting the products of the glycolysis (Figure 4). In contrast, iron processing and oxidative stress responses were down-regulated as oxidative stress was reduced (Figure 6). As expected, the aerobic part of the TCA-cycle was down-regulated. The need to generate essential compounds and amino acids was indicated by an elevated level of the aspartate metabolism (Figure 7). An indirect effect of the oxygen rich to oxygen deprived conditions was the up-regulation of the histidine biosynthesis (Figure 7). Histidine may function as a buffer for produced acids accumulating in the batch culture. In the following, these findings are described in detail.

Bottom Line: 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.Furthermore, our approach revealed a down-regulation in iron processing as well as the up-regulation of the histidine biosynthesis pathway.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. g.schramm@dkfz.de <g.schramm@dkfz.de>

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.

Show MeSH
Related in: MedlinePlus