title: Hierarchical analysis of dependency in metabolic networks.
abstract: BACKGROUND
  Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size.
  
  
  RESULTS
  We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego, http://gcrg.ucsd.edu/organisms/ecoli.html, 'model v 1.01. reactions') against accepted biochemical annotations, we provide the first systematic synopsis of an organism's metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation.
  
  
  BACKGROUND
  Source code, data sets and supplementary information are available at http://www.mas.ecp.fr/labo/equipe/gagneur/hierarchy/hierarchy.html
authors.affiliation: Lion Bioscience AG, Waldhoferstr. 98, 69123 Heidelberg, Germany. julien.gagneur@cellzome.com
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.forename: David B
authors.initials: DB
authors.lastname: Jackson
authors.forename: Georg
authors.initials: G
authors.lastname: Casari
mesh_terms: D000465:Algorithms; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008660:Metabolism / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D009097:Multienzyme Complexes / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D013269:Stochastic Processes
chemical_list: D009097:Multienzyme Complexes