Structural robustness of metabolic networks with respect to multiple knockouts

We present a generalised framework for analysing structural robustness of metabolic networks, based on the concept of elementary flux modes (EFMs). Extending our earlier study on single knockouts [Wilhelm, T., Behre, J., Schuster, S., 2004. Analysis of structural robustness of metabolic networks. IE...

Full description

Saved in:
Bibliographic Details
Published in:Journal of theoretical biology 2008-06, Vol.252 (3), p.433-441
Main Authors: Behre, Jörn, Wilhelm, Thomas, von Kamp, Axel, Ruppin, Eytan, Schuster, Stefan
Format: Article
Language:English
Subjects:
Amino Acids - biosynthesis
Elementary flux modes
Erythrocyte metabolism
Erythrocytes - metabolism
Escherichia coli
Escherichia coli - metabolism
Hepatocyte metabolism
Hepatocytes - metabolism
Humans
Metabolic Networks and Pathways - genetics
Metabolic Networks and Pathways - physiology
Models, Biological
Robustness measure
Sequence Deletion
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We present a generalised framework for analysing structural robustness of metabolic networks, based on the concept of elementary flux modes (EFMs). Extending our earlier study on single knockouts [Wilhelm, T., Behre, J., Schuster, S., 2004. Analysis of structural robustness of metabolic networks. IEE Proc. Syst. Biol. 1(1), 114–120], we are now considering the general case of double and multiple knockouts. The robustness measures are based on the ratio of the number of remaining EFMs after knockout vs. the number of EFMs in the unperturbed situation, averaged over all combinations of knockouts. With the help of simple examples we demonstrate that consideration of multiple knockouts yields additional information going beyond single-knockout results. It is proven that the robustness score decreases as the knockout depth increases. We apply our extended framework to metabolic networks representing amino acid anabolism in Escherichia coli and human hepatocytes, and the central metabolism in human erythrocytes. Moreover, in the E. coli model the two subnetworks synthesising amino acids that are essential and those that are non-essential for humans are studied separately. The results are discussed from an evolutionary viewpoint. We find that E. coli has the most robust metabolism of all the cell types studied here. Considering only the subnetwork of the synthesis of non-essential amino acids, E. coli and the human hepatocyte show about the same robustness.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2007.09.043