Pathway identification by network pruning in the metabolic network of Escherichia coli

MOTIVATION All metabolic networks contain metabolites, such as ATP and NAD, known as currency metabolites, which take part in many reactions. These are often removed in the study of these networks, but no consensus exists on what actually constitutes a currency metabolite, and it is also unclear how these highly connected nodes contribute to the global structure of the network. RESULTS In this article, we analyse how the Escherichia coli metabolic network responds to pruning in the form of sequential removal of metabolites with highest degree. As expected this leads to network fragmentation, but the process by which it occurs suggests modularity and long-range correlations within the network. We find that the pruned networks contain longer paths than the random expectation, and that the paths that survive the pruning also exhibit a lower cost (number of involved metabolites) compared with random paths in the full metabolic network. Finally we confirm that paths detected by pruning overlap with known metabolic pathways. We conclude that pruning reveals functional pathways in metabolic networks, where currency metabolites may be seen as ingredients in a well-balanced soup in which main metabolic production lines are immersed. CONTACT gerlee@nbi.dk SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

[1]  Francisco J. Planes,et al.  Recovering metabolic pathways via optimization , 2007, Bioinform..

[2]  S. Wodak,et al.  Inferring meaningful pathways in weighted metabolic networks. , 2006, Journal of molecular biology.

[3]  Thomas Pfeiffer,et al.  Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae , 2002, Bioinform..

[4]  D. Fell,et al.  Fat synthesis in adipose tissue. An examination of stoichiometric constraints. , 1986, The Biochemical journal.

[5]  B. Palsson,et al.  Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. , 2003, Genome research.

[6]  Michalis Faloutsos,et al.  Power laws and the AS-level internet topology , 2003, TNET.

[7]  Hierarchical Organization of Modularity in Metabolic Networks Supporting Online Material , 2002 .

[8]  A. Barabasi,et al.  Hierarchical Organization of Modularity in Metabolic Networks , 2002, Science.

[9]  Massimo Marchiori,et al.  Error and attacktolerance of complex network s , 2004 .

[10]  D S Callaway,et al.  Network robustness and fragility: percolation on random graphs. , 2000, Physical review letters.

[11]  D. Fell,et al.  The small world of metabolism , 2000, Nature Biotechnology.

[12]  Marek S. Skrzypek,et al.  YPDTM, PombePDTM and WormPDTM: model organism volumes of the BioKnowledgeTM Library, an integrated resource for protein information , 2001, Nucleic Acids Res..

[13]  An-Ping Zeng,et al.  The Connectivity Structure, Giant Strong Component and Centrality of Metabolic Networks , 2003, Bioinform..

[14]  Andrei Z. Broder,et al.  Graph structure in the Web , 2000, Comput. Networks.

[15]  Albert-László Barabási,et al.  Error and attack tolerance of complex networks , 2000, Nature.

[16]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[17]  Peter D. Karp,et al.  Multidimensional annotation of the Escherichia coli K-12 genome , 2007, Nucleic acids research.

[18]  Kim Sneppen,et al.  The cost and capacity of signaling in the Escherichia coli protein reaction network , 2008 .

[19]  S. Mangan,et al.  Structure and function of the feed-forward loop network motif , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Guimerà,et al.  Functional cartography of complex metabolic networks , 2005, Nature.

[21]  Stefan Schuster,et al.  A method for classifying metabolites in topological pathway analyses based on minimization of pathway number. , 2003, Bio Systems.

[22]  An-Ping Zeng,et al.  Decomposition of metabolic network into functional modules based on the global connectivity structure of reaction graph , 2004, Bioinform..

[23]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[24]  R. Heinrich,et al.  The Regulation of Cellular Systems , 1996, Springer US.

[25]  Markus J. Herrgård,et al.  A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology , 2008, Nature Biotechnology.

[26]  Petter Holme,et al.  Currency and commodity metabolites: their identification and relation to the modularity of metabolic networks. , 2006, IET systems biology.

[27]  Monica L. Mo,et al.  Global reconstruction of the human metabolic network based on genomic and bibliomic data , 2007, Proceedings of the National Academy of Sciences.

[28]  R. Tsien,et al.  Specificity and Stability in Topology of Protein Networks , 2022 .

[29]  Christoph Kaleta,et al.  Metabolic Pathway Analysis : from small to genome-scale networks , 2011 .