Systematic integration of experimental data and models in systems biology

BackgroundThe behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources.ResultsTaverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis.ConclusionsDistributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

[1]  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..

[2]  Matthew R. Pocock,et al.  Taverna: a tool for the composition and enactment of bioinformatics workflows , 2004, Bioinform..

[3]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[4]  Kara Dolinski,et al.  Saccharomyces genome database: Underlying principles and organisation , 2004, Briefings Bioinform..

[5]  Pedro Mendes,et al.  The markup is the model: reasoning about systems biology models in the Semantic Web era. , 2008, Journal of theoretical biology.

[6]  Douglas B. Kell,et al.  The role of modeling in systems biology , 2005 .

[7]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[8]  Norman W. Paton,et al.  SBRML: a markup language for associating systems biology data with models , 2010, Bioinform..

[9]  Douglas B. Kell,et al.  Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation , 1998, Bioinform..

[10]  Richard Côté,et al.  The PRIDE proteomics identifications database: data submission, query, and dataset comparison. , 2008, Methods in molecular biology.

[11]  Yanli Wang,et al.  PubChem: Integrated Platform of Small Molecules and Biological Activities , 2008 .

[12]  Jacky L. Snoep,et al.  Web-based kinetic modelling using JWS Online , 2004, Bioinform..

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

[14]  Yukiko Matsuoka,et al.  Integration of CellDesigner and SABIO-RK , 2007, Silico Biol..

[15]  Michel Schneider,et al.  The UniProtKB/Swiss-Prot knowledgebase and its Plant Proteome Annotation Program. , 2009, Journal of proteomics.

[16]  Matthias Stein,et al.  SYCAMORE - a systems biology computational analysis and modeling research environment , 2008, Bioinform..

[17]  Renate Kania,et al.  Storing and Annotating of Kinetic Data , 2007, Silico Biol..

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

[19]  B O Palsson,et al.  Metabolic modeling of microbial strains in silico. , 2001, Trends in biochemical sciences.

[20]  Neil Swainston,et al.  libAnnotationSBML: a library for exploiting SBML annotations , 2009, Bioinform..

[21]  Uwe Scholz,et al.  An Integration and Analysis Pipeline for Systems Biology in Crop Plant Metabolism , 2009, DILS.

[22]  D. Kell,et al.  Schemes of flux control in a model of Saccharomyces cerevisiae glycolysis. , 2002, European journal of biochemistry.

[23]  BMC Bioinformatics , 2005 .

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

[25]  Douglas B. Kell,et al.  Automated manipulation of systems biology models using libSBML within Taverna workflows , 2008, Bioinform..

[26]  Julia Handl,et al.  Streamlining the construction of large-scale dynamic models using generic kinetic equations , 2010, Bioinform..

[27]  D. Kell.  Systems biology, metabolic modelling and metabolomics in drug discovery and development. , 2006, Drug discovery today.

[28]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[29]  Pedro Mendes,et al.  Design and Architecture of Web Services for Simulation of Biochemical Systems , 2009, DILS.

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

[31]  Carole A. Goble,et al.  Taverna: a tool for building and running workflows of services , 2006, Nucleic Acids Res..

[32]  Neil Swainston,et al.  Integration of metabolic databases for the reconstruction of genome-scale metabolic networks , 2010, BMC Systems Biology.

[33]  Andrew Hayes,et al.  Hybridization array technology coupled with chemostat culture: Tools to interrogate gene expression in Saccharomyces cerevisiae. , 2002, Methods.

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

[35]  Nigel W. Hardy,et al.  MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics , 2006, BMC Bioinformatics.

[36]  Vipul Periwal,et al.  System Modeling in Cellular Biology: From Concepts to Nuts and Bolts , 2006 .

[37]  Barbara M. Bakker,et al.  Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. , 2000, European journal of biochemistry.

[38]  Carmen G. Moles,et al.  Parameter estimation in biochemical pathways: a comparison of global optimization methods. , 2003, Genome research.

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

[40]  Hugh D. Spence,et al.  Minimum information requested in the annotation of biochemical models (MIRIAM) , 2005, Nature Biotechnology.

[41]  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.

[42]  Neil Swainston,et al.  Enzyme kinetics informatics: from instrument to browser , 2010, The FEBS journal.

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

[44]  H M Davey,et al.  Oscillatory, stochastic and chaotic growth rate fluctuations in permittistatically controlled yeast cultures. , 1996, Bio Systems.