Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms

MOTIVATION Information from fully sequenced genomes makes it possible to reconstruct strain-specific global metabolic network for structural and functional studies. These networks are often very large and complex. To properly understand and analyze the global properties of metabolic networks, methods for rationally representing and quantitatively analyzing their structure are needed. RESULTS In this work, the metabolic networks of 80 fully sequenced organisms are in silico reconstructed from genome data and an extensively revised bioreaction database. The networks are represented as directed graphs and analyzed by using the 'breadth first searching algorithm to identify the shortest pathway (path length) between any pair of the metabolites. The average path length of the networks are then calculated and compared for all the organisms. Different from previous studies the connections through current metabolites and cofactors are deleted to make the path length analysis physiologically more meaningful. The distribution of the connection degree of these networks is shown to follow the power law, indicating that the overall structure of all the metabolic networks has the characteristics of a small world network. However, clear differences exist in the network structure of the three domains of organisms. Eukaryotes and archaea have a longer average path length than bacteria. AVAILABILITY The reaction database in excel format and the programs in VBA (Visual Basic for Applications) are available upon request. SUPPLEMENTARY MATERIAL Bioinformatics Online.

[1]  Lada A. Adamic,et al.  Power-Law Distribution of the World Wide Web , 2000, Science.

[2]  Peter D. Karp,et al.  The EcoCyc Database , 2002, Nucleic Acids Res..

[3]  Natalia Maltsev,et al.  WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction , 2000, Nucleic Acids Res..

[4]  A. Barabasi,et al.  Comparable system-level organization of Archaea and Eukaryotes , 2001, Nature Genetics.

[5]  B. Palsson,et al.  Assessment of the metabolic capabilities of Haemophilus influenzae Rd through a genome-scale pathway analysis. , 2000, Journal of theoretical biology.

[6]  B. Palsson,et al.  Toward Metabolic Phenomics: Analysis of Genomic Data Using Flux Balances , 1999, Biotechnology progress.

[7]  Vladimir Batagelj,et al.  Pajek - Program for Large Network Analysis , 1999 .

[8]  B. Palsson,et al.  Metabolic modelling of microbes: the flux-balance approach. , 2002, Environmental microbiology.

[9]  D. Fell,et al.  Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering. , 1999, Trends in biotechnology.

[10]  F. Neidhardt,et al.  Physiology of the bacterial cell : a molecular approach , 1990 .

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

[12]  Albert-László Barabási,et al.  Statistical mechanics of complex networks , 2001, ArXiv.

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

[14]  Susumu Goto,et al.  LIGAND: chemical database for enzyme reactions , 1998, Bioinform..

[15]  Susumu Goto,et al.  The KEGG databases at GenomeNet , 2002, Nucleic Acids Res..

[16]  D. Fell,et al.  A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks , 2000, Nature Biotechnology.

[17]  R. Heinrich,et al.  Metabolic Pathway Analysis: Basic Concepts and Scientific Applications in the Post‐genomic Era , 1999, Biotechnology progress.

[18]  S. Strogatz Exploring complex networks , 2001, Nature.

[19]  M. Huynen,et al.  The frequency distribution of gene family sizes in complete genomes. , 1998, Molecular biology and evolution.

[20]  Susumu Goto,et al.  LIGAND: database of chemical compounds and reactions in biological pathways , 2002, Nucleic Acids Res..

[21]  Thomas Lengauer,et al.  Pathway analysis in metabolic databases via differetial metabolic display (DMD) , 2000, German Conference on Bioinformatics.

[22]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[23]  Jason A. Papin,et al.  Determination of redundancy and systems properties of the metabolic network of Helicobacter pylori using genome-scale extreme pathway analysis. , 2002, Genome research.

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

[25]  中尾 光輝,et al.  KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース) , 2000 .

[26]  B. Palsson,et al.  Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. , 2000, Journal of theoretical biology.

[27]  Susumu Goto,et al.  LIGAND: chemical database of enzyme reactions , 2000, Nucleic Acids Res..