Metabolic reconstruction, constraint-based analysis and game theory to probe genome-scale metabolic networks.

With the advent of modern omics technologies, it has become feasible to reconstruct (quasi-) whole-cell metabolic networks and characterize them in more and more detail. Computer simulations of the dynamic behavior of such networks are difficult due to a lack of kinetic data and to computational limitations. In contrast, network analysis based on appropriate constraints such as the steady-state condition (constraint-based analysis) is feasible and allows one to derive conclusions about the system's metabolic capabilities. Here, we review methods for the reconstruction of metabolic networks, modeling techniques such as flux balance analysis and elementary flux modes and current progress in their development and applications. Game-theoretical methods for studying metabolic networks are discussed as well.

[1]  Erwin P. Gianchandani,et al.  Flux balance analysis in the era of metabolomics , 2006, Briefings Bioinform..

[2]  Steffen Klamt,et al.  CASOP: a computational approach for strain optimization aiming at high productivity. , 2010, Journal of biotechnology.

[3]  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.

[4]  James A. Barnett,et al.  Glucose Catabolism in Yeast and Muscle , 2005 .

[5]  V. Wendisch.  Amino acid biosynthesis : pathways, regulation and metabolic engineering , 2007 .

[6]  F. Srienc,et al.  Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolism , 2009, Applied Microbiology and Biotechnology.

[7]  Bas Teusink,et al.  Understanding the Adaptive Growth Strategy of Lactobacillus plantarum by In Silico Optimisation , 2009, PLoS Comput. Biol..

[8]  D. Fell,et al.  A Genome-Scale Metabolic Model of Arabidopsis and Some of Its Properties1[C][W] , 2009, Plant Physiology.

[9]  Eytan Ruppin,et al.  Integrating quantitative proteomics and metabolomics with a genome-scale metabolic network model , 2010, Bioinform..

[10]  Isaac Meilijson,et al.  Can single knockouts accurately single out gene functions? , 2008, BMC Systems Biology.

[11]  B. Palsson,et al.  Metabolic capabilities of Escherichia coli: I. synthesis of biosynthetic precursors and cofactors. , 1993, Journal of theoretical biology.

[12]  Bernhard O. Palsson,et al.  Gene Expression Profiling and the Use of Genome-Scale In Silico Models of Escherichia coli for Analysis: Providing Context for Content , 2009, Journal of bacteriology.

[13]  J. Stelling,et al.  Robustness of Cellular Functions , 2004, Cell.

[14]  S. Schuster,et al.  ON ELEMENTARY FLUX MODES IN BIOCHEMICAL REACTION SYSTEMS AT STEADY STATE , 1994 .

[15]  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.

[16]  Mark G. Poolman,et al.  A Genome-scale Metabolic Model of Arabidopsis , 2009 .

[17]  P. May,et al.  ChlamyCyc: an integrative systems biology database and web-portal for Chlamydomonas reinhardtii , 2009, BMC Genomics.

[18]  O. Demin,et al.  The Edinburgh human metabolic network reconstruction and its functional analysis , 2007, Molecular systems biology.

[19]  J. Kreft,et al.  Biofilms promote altruism. , 2004, Microbiology.

[20]  U. Sauer,et al.  A Novel Metabolic Cycle Catalyzes Glucose Oxidation and Anaplerosis in Hungry Escherichia coli* , 2003, Journal of Biological Chemistry.

[21]  Peer Bork,et al.  Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation , 2007, Bioinform..

[22]  Andrea Sackmann,et al.  Modularization of biochemical networks based on classification of Petri net t-invariants , 2008, BMC Bioinformatics.

[23]  B. Palsson.  Systems Biology: Properties of Reconstructed Networks , 2006 .

[24]  U. Sauer,et al.  Article number: 62 REVIEW Metabolic networks in motion: 13 C-based flux analysis , 2022 .

[25]  Roded Sharan,et al.  Decoupling Environment-Dependent and Independent Genetic Robustness across Bacterial Species , 2010, PLoS Comput. Biol..

[26]  J. C. Aledo,et al.  Switching Between Cooperation and Competition in the Use of Extracellular Glucose , 2007, Journal of Molecular Evolution.

[27]  B. Palsson,et al.  Candidate Metabolic Network States in Human Mitochondria , 2005, Journal of Biological Chemistry.

[28]  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.

[29]  D. Fell,et al.  Challenges to be faced in the reconstruction of metabolic networks from public databases. , 2006, Systems biology.

[30]  S. Schuster,et al.  Understanding the roadmap of metabolism by pathway analysis. , 2007, Methods in molecular biology.

[31]  Jason A. Papin,et al.  Metabolic network analysis integrated with transcript verification for sequenced genomes , 2009, Nature Methods.

[32]  Markus J. Herrgård,et al.  Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. , 2004, Genome research.

[33]  Dong-Yup Lee,et al.  Genome-scale modeling and in silico analysis of mouse cell metabolic network. , 2009, Molecular bioSystems.

[34]  E. Ruppin,et al.  Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism , 2010, Molecular systems biology.

[35]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[36]  Kyongbum Lee,et al.  Metabolic flux analysis of cultured hepatocytes exposed to plasma , 2003, Biotechnology and bioengineering.

[37]  Harvey J. Greenberg,et al.  Reconstruction and Functional Characterization of the Human Mitochondrial Metabolic Network Based on Proteomic and Biochemical Data* , 2004, Journal of Biological Chemistry.

[38]  Markus J. Herrgård,et al.  Network-based prediction of human tissue-specific metabolism , 2008, Nature Biotechnology.

[39]  A. Veiga,et al.  Cyanide-resistant respiration is frequent, but confined to yeasts incapable of aerobic fermentation. , 2000, FEMS microbiology letters.

[40]  Adam M. Feist,et al.  Reconstruction of biochemical networks in microorganisms , 2009, Nature Reviews Microbiology.

[41]  E. Ruppin,et al.  Multiple knockout analysis of genetic robustness in the yeast metabolic network , 2006, Nature Genetics.

[42]  S. Schuster,et al.  Structural robustness of metabolic networks with respect to multiple knockouts. , 2008, Journal of theoretical biology.

[43]  Stephen S Fong,et al.  Metabolic gene–deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes , 2004, Nature Genetics.

[44]  G. Stephanopoulos,et al.  Metabolic Engineering: Principles And Methodologies , 1998 .

[45]  Jason A. Papin,et al.  Comparison of network-based pathway analysis methods. , 2004, Trends in biotechnology.

[46]  S. Oliver,et al.  Plasticity of genetic interactions in metabolic networks of yeast , 2007, Proceedings of the National Academy of Sciences.

[47]  A. Barabasi,et al.  Blueprint for antimicrobial hit discovery targeting metabolic networks , 2010, Proceedings of the National Academy of Sciences.

[48]  C. Schilling,et al.  Flux coupling analysis of genome-scale metabolic network reconstructions. , 2004, Genome research.

[49]  D. Fell,et al.  Is maximization of molar yield in metabolic networks favoured by evolution? , 2008, Journal of theoretical biology.

[50]  J. Schwender,et al.  Rubisco without the Calvin cycle improves the carbon efficiency of developing green seeds , 2004, Nature.

[51]  Bernhard O. Palsson,et al.  Context-Specific Metabolic Networks Are Consistent with Experiments , 2008, PLoS Comput. Biol..

[52]  S. Schuster,et al.  Cooperation and cheating in microbial exoenzyme production--theoretical analysis for biotechnological applications. , 2010, Biotechnology journal.

[53]  Angel Rubio,et al.  Computing the shortest elementary flux modes in genome-scale metabolic networks , 2009, Bioinform..

[54]  S. Schuster,et al.  Can the whole be less than the sum of its parts? Pathway analysis in genome-scale metabolic networks using elementary flux patterns. , 2009, Genome research.

[55]  S. Bonhoeffer,et al.  Cooperation and Competition in the Evolution of ATP-Producing Pathways , 2001, Science.

[56]  Ali R. Zomorrodi,et al.  Genome-scale gene/reaction essentiality and synthetic lethality analysis , 2009, Molecular systems biology.

[57]  Adam M. Feist,et al.  A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information , 2007, Molecular systems biology.

[58]  S. Schuster,et al.  Game-theoretical approaches to studying the evolution of biochemical systems. , 2005, Trends in biochemical sciences.

[59]  Jan-Ulrich Kreft,et al.  Use of Game-Theoretical Methods in Biochemistry and Biophysics , 2008, Journal of biological physics.

[60]  David A. Fell,et al.  Detection of stoichiometric inconsistencies in biomolecular models , 2008, Bioinform..

[61]  A. Barabasi,et al.  Targets Drug Genomes Identify Novel Antimicrobial Staphylococcus Aureus of Multiple Reconstruction and Flux Balance Analysis Comparative Genome-scale Metabolic Supplemental Material , 2009 .

[62]  B. Palsson,et al.  A protocol for generating a high-quality genome-scale metabolic reconstruction , 2010 .

[63]  Kim Marriott,et al.  A generic algorithm for layout of biological networks , 2009, BMC Bioinformatics.

[64]  Gary D Bader,et al.  The Genetic Landscape of a Cell , 2010, Science.

[65]  C. Wittmann,et al.  The l -Lysine Story: From Metabolic Pathways to Industrial Production , 2007 .

[66]  Duygu Dikicioglu,et al.  Flux Balance Analysis of a Genome‐Scale Yeast Model Constrained by Exometabolomic Data Allows Metabolic System Identification of Genetically Different Strains , 2007, Biotechnology progress.

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

[68]  Kyongbum Lee,et al.  Utilizing elementary mode analysis, pathway thermodynamics, and a genetic algorithm for metabolic flux determination and optimal metabolic network design , 2010, BMC Systems Biology.

[69]  U. Sauer,et al.  Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network robustness to null mutations in yeast , 2005, Genome Biology.

[70]  D. Greig,et al.  The Prisoner's Dilemma and polymorphism in yeast SUC genes , 2004, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[71]  Jason A. Papin,et al.  Applications of genome-scale metabolic reconstructions , 2009, Molecular systems biology.

[72]  A. van Oudenaarden,et al.  Snowdrift game dynamics and facultative cheating in yeast , 2009, Nature.

[73]  Bernhard O. Palsson,et al.  Identification of Genome-Scale Metabolic Network Models Using Experimentally Measured Flux Profiles , 2006, PLoS Comput. Biol..

[74]  L. Quek,et al.  AraGEM, a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis1[W] , 2009, Plant Physiology.

[75]  G. Church,et al.  Modular epistasis in yeast metabolism , 2005, Nature Genetics.

[76]  J. Nielsen,et al.  Integration of metabolome data with metabolic networks reveals reporter reactions , 2006, Molecular systems biology.

[77]  B. Palsson,et al.  Genome-scale models of microbial cells: evaluating the consequences of constraints , 2004, Nature Reviews Microbiology.

[78]  R Heinrich,et al.  Metabolic regulation and mathematical models. , 1977, Progress in biophysics and molecular biology.

[79]  L. Nielsen,et al.  Modeling Hybridoma Cell Metabolism Using a Generic Genome‐Scale Metabolic Model of Mus musculus , 2008, Biotechnology progress.

[80]  E. Ruppin,et al.  Predicting metabolic biomarkers of human inborn errors of metabolism , 2009, Molecular systems biology.

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

[82]  U. Sauer,et al.  Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli , 2007, Molecular systems biology.

[83]  F. Srienc,et al.  Minimal Escherichia coli Cell for the Most Efficient Production of Ethanol from Hexoses and Pentoses , 2008, Applied and Environmental Microbiology.

[84]  Miguel Rocha,et al.  OptFlux: an open-source software platform for in silico metabolic engineering , 2010, BMC Systems Biology.

[85]  B. Palsson,et al.  Towards multidimensional genome annotation , 2006, Nature Reviews Genetics.