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An Automatic Translation of SBML into Beta-Binders
January-March 2008 (vol. 5 no. 1)
pp. 80-90
A translation of SBML (Systems Biology Markup Language) into a process algebra is proposed in order to allow the formal specification, the simulation and the formal analysis of biological models. Beta-binders, a language with a quantitative stochastic extension, is chosen for the translation. The proposed translation focuses on the main components of SBML models, as species and reactions. Furthermore, it satisfies the compositional property, i.e. the translation of the whole model is obtained by composing the translation of the subcomponents. An automatic translator tool of SBML models into Beta-binders has been implemented as well. Finally, the translation of a simple model is reported.

[1] H. Kitano, “Systems Biology: A Brief Overview,” Science, vol. 295, no. 5560, pp. 1662-1664, 2002.
[2] C. Priami, A. Regev, W. Silverman, and E. Shapiro, “Application of a Stochastic Name-Passing Calculus to Representation and Simulation of Molecular Processes,” Information Processing Letters, vol. 80, no. 1, pp. 25-31, 2001.
[3] A. Regev, E.M. Panina, W. Silverman, L. Cardelli, and E. Shapiro, “BioAmbients: An Abstraction for Biological Compartments,” Theoretical Computer Science, vol. 325, no. 1, pp. 141-167, 2004.
[4] V. Danos and C. Laneve, “Core Formal Molecular Biology,” Proc. European Symp. Programming (ESOP '03), pp. 302-318, 2003.
[5] M. Nagasaki, S. Onami, S. Miyano, and H. Kitano, “Bio-Calculus: Its Concept and Molecular Interaction,” Genome Informatics, vol. 10, pp. 133-143, 1999.
[6] M. Calder, S. Gilmore, and J. Hillston, “Modeling the Influence of RKIP on the ERK Signalling Pathway Using the Stochastic Process Algebra PEPA,” Proc. Computational Methods in Systems Biology (CMSB '04), 2004.
[7] BIOSPI Project,, June 2006.
[8] A. Phillips, “SPIM, The Stochastic Pi-Machine,” www.doc.ic., 2006.
[9] C. Kuttler, J. Niehren, and R. Blossey, “Gene Regulation in the $\pi\hbox{-}{\rm calculus}$ : Simulating Cooperativity at the Lambda Switch,” Proc. Second Int'l Workshop Concurrent Models in Molecular Biology (BioConcur '04), 2004.
[10] P. Lecca, C. Priami, P. Quaglia, B. Rossi, C. Laudanna, and G. Costantin, “Language Modeling and Simulation of Autoreactive Lymphocytes Recruitment in Inflamed Brain Vessels,” SIMULATION: Trans. Soc. for Modeling and Simulation Int'l, vol. 80, pp. 273-288, 2004.
[11] M. Hucka, A. Finney, B.J. Bornstein, S.M. Keating, B.E. Shapiro, J. Matthews, B.L. Kovitz, M.J. Schilstra, A. Funahashi, J.C. Doyle, and H. Kitano, “Evolving a Lingua Franca and Associated Software Infrastructure for Computational Systems Biology: The Systems Biology Markup Language (SBML) Project,” Systems Biology, vol. 1, no. 1, June 2004.
[12] N. Le Novére, B. Bornstein, A. Broicher, M. Courtot, M. Donizelli, H. Dharuri, L. Li, H. Sauro, M. Schilstra, B. Shapiro, J.L. Snoep, and M. Hucka, “BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems,” Nucleic Acids Research, vol. 34, pp. D689-D691, 2006.
[13] B.G. Oliver and J.L. Snoep, “Web-Based Kinetic Modelling Using JWS Online,” Bioinformatics, vol. 20, no. 13, pp. 2143-2144, 2004.
[14] M. Kanehisa and S. Goto, “KEGG: Kyoto Encyclopedia of Genes and Genomes,” Nucleic Acids Research, vol. 28, no. 1, pp. 27-30, Jan. 2000.
[15] Z. Dong, X. Dong, X. Xu, Y. Fu, Z. Zhang, and L. He, “An Implementation for Mapping SBML to BioSPI,” Proc. Int'l Conf. Fuzzy Systems and Knowledge Discovery (FSKD '05), Electronic Notes in Artificial Intelligence, no. 3614, pp. 1128-1131, 2005.
[16] C. Eccher and C. Priami, “Design and Implementation of a Tool for Translating SBML into the Biochemical Stochastic $\pi\hbox{-}{\rm Calculus}$ ,” Bioinformatics, vol. 22, no. 24, pp. 3075-3081, 2006.
[17] “PNK (Petri Net Kernel) 2e,” index.html, 2005.
[18] N. Chabrier, F. Fages, and S. Soliman, “The Biochemical Abstract Machine BIOCHAM,” Proc. Workshop Computational Methods in Systems Biology (CMSB '04), 2004.
[19] F.A. Kolpakov, “BIOUML—Framework for Visual Modeling and Simulation Biological Systems,” Proc. Int'l Conf. Bioinformatics of Genome Regulation and Structure (BGRS '02), 2002.
[20] C. Priami and P. Quaglia, “Beta Binders for Biological Interactions,” Proc. Computational Methods in Systems Biology (CMSB '04), 2004.
[21] F. Ciocchetta, C. Priami, and P. Quaglia, “Modeling Kohn Interaction Maps with Beta-Binders: An Example,” Trans. Computational Systems Biology, vol. 3, pp. 33-48, 2005.
[22] SBML Homepage, http:/, Dec. 2005.
[23] A. Finney and M. Hucka, “Systems Biology Markup Language (SBML) Level 2: Structures and Facilities for Model Definitions,” http://sbml.orgdocuments/, 2003.
[24] R. Milner, Communicating and Mobile Systems: The $\pi\hbox{-}{\rm calculus}$ . Cambridge Univ. Press, 1999.
[25] D.T. Gillespie, “Exact Stochastic Simulation of Coupled Chemical Reactions,” J. Physical Chemistry, vol. 81, no. 25, pp. 2340-2361, 1977.
[26] P. Degano, D. Prandi, C. Priami, and P. Quaglia, “Beta Binders for Biological Quantitative Experiments,” Proc. Int'l Workshop Quantitative Aspects of Programming Languages (QAPL'06), Electronic Notes in Theoretical Computer Science, vol. 164, no. 3, pp. 101-117, 2006.
[27] F. Ciocchetta and C. Priami, “Beta-Binders with Biological Trans.,” Technical Report TR-10-2006, The Microsoft Research—Univ. of Trento Centre for Computational and Systems Biology, 2006.
[28] C.V. Rao and A.P. Arkin, “Stochastic Chemical Kinetics and the Quasi-Steady-State Assumption: Application to the Gillespie Algorithm,” J. Chemical Physics, vol. 11, no. 11, 2003.
[29] E.L. Haseltine and J.B. Rawlings, “Approximate Simulation of Coupled Fast and Slow Reactions for Stochastic Chemical Kinetics,” J. Chemical Physics, vol. 117, pp. 6959-6969, 2006.
[30] Y. Cao, D.T. Gillespie, and L. Petzold, “Accelerated Stochastic Simulation of the Stiff Enzyme-Substrate Reaction,” J. Chemical Physics, vol. 123, no. 14, pp. 144917-144929, 2005.
[31] Y. Cao, D.T. Gillespie, and L. Petzold, “Multiscale Stochastic Simulation Algorithm with Stochastic Partial Equilibrium Assumption for Chemically Reacting Systems,” J. Computational Physics, vol. 206, pp. 395-411, 2005.
[32] A.M. Kierzek, “STOCKS: STOChastic Kinetics Simulations of Biochemical Systems with Gillespie Algorithm,” Bioinformatics, vol. 18, pp. 470-481, 2002.
[33] R. Bundschuh, F. Hayot, and C. Jayaprakash, “Fluctuations and Slow Variables in Genetic Networks,” Biophysical J., vol. 84, no. 3, pp. 1606-1615, 2003.
[34] I.H. Segel, Enzyme Kinetics: Behaviour and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. Wiley-Interscience, 1993.
[35] “The Objective Caml System,” http:/, 2006.
[36] S.J. Edelstein, O. Schaad, E. Henry, D. Bertrand, and J.P. Changgeux, “A Kinetic Mechanism for Nicotin Acetylcholine Receptors Based on Multiple Allosteric Transitions,” Biological Cybernetics, no. 75, pp. 361-379, 1996.
[37] N. Le Novére and T.S. Shimizu, “StochSim: Modelling of Stochastic Biomolecular Processes,” Bioinformatics, vol. 17, pp.575-576, 2001.

Index Terms:
Process algebras, biological systems, modeling, Systems Biology Markup Language (SBML), translation tool, systems biology
Federica Ciocchetta, Corrado Priami, Paola Quaglia, "An Automatic Translation of SBML into Beta-Binders," IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 5, no. 1, pp. 80-90, Jan.-March 2008, doi:10.1109/TCBB.2007.70219
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