ReMatch: a web-based tool to construct, store and share stoichiometric metabolic models with carbon maps for metabolic flux analysis

Summar y ReMatch is a web-based, user-friendly tool that constructs stoichiometric network models for metabolic flux analysis, integrating user-developed models into a database collected from several comprehensive metabolic data resources, including KEGG, MetaCyc and CheBI. Particularly, ReMatch augments the metabolic reactions of the model with carbon mappings to facilitate 13C metabolic flux analysis. The construction of a network model consisting of biochemical reactions is the first step in most metabolic modelling tasks. This model construction can be a tedious task as the required information is usually scattered to many separate databases whose interoperability is suboptimal, due to the heterogeneous naming conventions of metabolites in different databases. Another, particularly severe data integration problem is faced in 13C metabolic flux analysis, where the mappings of carbon atoms from substrates into products in the model are required. ReMatch has been developed to solve the above data integration problems. First, ReMatch matches the imported user-developed model against the internal ReMatch database while considering a comprehensive metabolite name thesaurus. This, together with wild card support, allows the user to specify the model quickly without having to look the names up manually. Second, ReMatch is able to augment reactions of the model with carbon mappings, obtained either from the internal database or given by the user with an easy-touse tool. The constructed models can be exported into 13C-FLUX and SBML file formats. Further, a stoichiometric matrix and visualizations of the network model can be generated. The constructed models of metabolic networks can be optionally made available to the other users of ReMatch. Thus, ReMatch provides a common repository for metabolic network models with carbon mappings for the needs of metabolic flux analysis community. ReMatch is freely available for academic use at http://www.cs.helsinki.fi/group/sysfys/software/rematch/.

[1]  B. Palsson,et al.  Metabolic Flux Balancing: Basic Concepts, Scientific and Practical Use , 1994, Bio/Technology.

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

[3]  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.

[4]  W Wiechert,et al.  A universal framework for 13C metabolic flux analysis. , 2001, Metabolic engineering.

[5]  W. Wiechert.  An introduction to 13C metabolic flux analysis. , 2002, Genetic engineering.

[6]  Karl Sanford,et al.  Genomics to fluxomics and physiomics - pathway engineering. , 2002, Current opinion in microbiology.

[7]  S. Schuster,et al.  Metabolic network structure determines key aspects of functionality and regulation , 2002, Nature.

[8]  Masanori Arita.  In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. , 2003, Genome research.

[9]  Kenneth J. Kauffman,et al.  Advances in flux balance analysis. , 2003, Current opinion in biotechnology.

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

[11]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[12]  J. L. Snoep,et al.  Java Web Simulation (JWS); A Web Based Database of Kinetic Models , 2004, Molecular Biology Reports.

[13]  Sarah M. Keating,et al.  Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project. , 2004, Systems biology.

[14]  U. Sauer,et al.  High-throughput metabolic flux analysis based on gas chromatography-mass spectrometry derived 13C constraints. , 2004, Analytical biochemistry.

[15]  Marc K Hellerstein,et al.  Stable isotope-mass spectrometric measurements of molecular fluxes in vivo: emerging applications in drug development. , 2004, Current opinion in molecular therapeutics.

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

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

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

[19]  Chunhui Li,et al.  Exploring the diversity of complex metabolic networks , 2005, Bioinform..

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

[21]  U. Sauer,et al.  Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism , 2005, Nature Genetics.

[22]  Peter D. Karp,et al.  EcoCyc: a comprehensive database resource for Escherichia coli , 2004, Nucleic Acids Res..

[23]  J. Heijnen,et al.  Metabolic-flux analysis of Saccharomyces cerevisiae CEN.PK113-7D based on mass isotopomer measurements of (13)C-labeled primary metabolites. , 2005, FEMS yeast research.

[24]  Gopal R. Gopinath,et al.  Reactome: a knowledge base of biologic pathways and processes , 2007, Genome Biology.

[25]  Jacky L. Snoep,et al.  BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems , 2005, Nucleic Acids Res..

[26]  Renate Kania,et al.  SABIO-RK: A data warehouse for biochemical reactions and their kinetics , 2007, J. Integr. Bioinform..

[27]  Wolfgang Wiechert,et al.  The topology of metabolic isotope labeling networks , 2007, BMC Bioinformatics.

[28]  Ralf Takors,et al.  Metabolic flux analysis at ultra short time scale: isotopically non-stationary 13C labeling experiments. , 2007, Journal of biotechnology.

[29]  Christina Backes,et al.  BNDB – The Biochemical Network Database , 2007, BMC Bioinformatics.

[30]  G. Stephanopoulos,et al.  Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions. , 2007, Metabolic engineering.

[31]  Michael Hucka,et al.  LibSBML: an API Library for SBML , 2008, Bioinform..

[32]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[33]  Juho Rousu,et al.  An analytic and systematic framework for estimating metabolic flux ratios from 13C tracer experiments , 2008, BMC Bioinformatics.

[34]  Michael Darsow,et al.  ChEBI: a database and ontology for chemical entities of biological interest , 2007, Nucleic Acids Res..