Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S., and Gilles, E.D.. "Metabolic network structure determines key aspects of functionality and regulation." Nature. 420
(6912).
2002.
pp. 190-3.
[ .pdf ] [ PubMed ]
The relationship between structure, function and regulation in complex cellular networks is a still largely open question. Systems biology aims to explain this relationship by combining experimental and theoretical approaches. Current theories have various strengths and shortcomings in providing an integrated, predictive description of cellular networks. Specifically, dynamic mathematical modelling of large-scale networks meets difficulties because the necessary mechanistic detail and kinetic parameters are rarely available. In contrast, structure-oriented analyses only require network topology, which is well known in many cases. Previous approaches of this type focus on network robustness or metabolic phenotype, but do not give predictions on cellular regulation. Here, we devise a theoretical method for simultaneously predicting key aspects of network functionality, robustness and gene regulation from network structure alone. This is achieved by determining and analysing the non-decomposable pathways able to operate coherently at steady state (elementary flux modes). We use the example of Escherichia coli central metabolism to illustrate the method.
Keywords: Biomass ; Cell Physiology ; Computational Biology ; Computer Simulation ; *Energy Metabolism ; Escherichia coli_genetics ; Escherichia coli_growth and development ; Escherichia coli_*metabolism ; Gene Expression Regulation Bacterial ; *Models Biological ; Phenotype ; Systems Theory
Schuster, S., Pfeiffer, T., Moldenhauer, F., Koch, I., and Dandekar, T.. "Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae." Bioinformatics. 18
(2).
2002.
pp. 351-61.
[ PubMed ] [ WebSite ]
MOTIVATION: Reconstructing and analyzing the metabolic map of microorganisms is an important challenge in bioinformatics. Pathway analysis of large metabolic networks meets with the problem of combinatorial explosion of pathways. Therefore, appropriate algorithms for an automated decomposition of these networks into smaller subsystems are needed. RESULTS: A decomposition algorithm for metabolic networks based on the local connectivity of metabolites is presented. Interrelations of this algorithm with alternative methods proposed in the literature and the theory of small world networks are discussed. The applicability of our method is illustrated by an analysis of the metabolism of Mycoplasma pneumoniae, which is an organism of considerable medical interest. The decomposition gives rise to 19 subnetworks. Three of these are here discussed in biochemical terms: arginine degradation, the tetrahydrofolate system, and nucleotide metabolism. The interrelations of pathway analysis of biochemical networks with Petri net theory are outlined.
Keywords: Algorithms ; Arginine_metabolism ; Computational Biology ; *Metabolism ; Models Biological ; Mycoplasma pneumoniae_*metabolism ; Nucleotides_metabolism ; *Software