Combinatorial Complexity of Pathway Analysis in Metabolic Networks
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Elementary flux mode analysis is a promising approach for a pathway-oriented perspective of metabolic networks. However, in larger networks it is hampered by the combinatorial explosion of possible routes. In this work we give some estimations on the combinatorial complexity including theoretical upper bounds for the number of elementary flux modes in a network of a given size. In a case study, we computed the elementary modes in the central metabolism of Escherichia coli while utilizing four different substrates. Interestingly, although the number of modes occurring in this complex network can exceed half a million, it is still far below the upper bound. Hence, to a certain extent, pathway analysis of central catabolism is feasible to assess network properties such as flexibility and functionality.
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- Edwards, J.S. and Palsson, B.O. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 5528–5533.Google Scholar
- Fell, D.A. and Wagner A. The small world of metabolism. Nat Biotechnol., 18 (2000) 1121–2.Google Scholar
- Heinrich, R. and Schuster, S.: The Regulation of Cellular Systems. Chapman & Hall, New York, 1996.Google Scholar
- Klamt, S., Schuster S. and Gilles E.D.: Calculability analysis in underdetermined metabolic networks illustrated by a model of the central metabolism in purple nonsulfur bacteria. Biotechnol. Bioeng. 77 (2002) 734–751.Google Scholar
- Schilling, C.H., Schuster, S., Palsson, B.O. and Heinrich, R.: Metabolic pathway analysis: Basic concepts and scientific applications in the post-genomic era. Biotechnol. Prog. 15 (1999) 296–303.Google Scholar
- Schuster, S., Dandekar, T. and Fell, D.A.: Detection of elementary flux modes in biochemical networks: A promising tool for pathway analysis and metabolic engineering. Trends Biotechnol. 17 (1999) 53–60.Google Scholar
- Schuster, S., Fell, D. and Dandekar, T.: A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nature Biotechnol. 18 (2000) 326–332.Google Scholar
- Schuster, S., Pfeiffer, T., Moldenhauer, F., Koch, I. and Dandekar, T.: Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumomniae. Bioinformatics, 18 (2002) 351–361.Google Scholar
- Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S. and Gilles, E.D.: Predicting key aspects of functionality and regulation from metabolic network structure. Submitted.Google Scholar
- Stephanopoulos, G.N., Aristidou, A., Nielsen, J.: Metabolic Engineering. Academic Press, San Diego, 1998.Google Scholar