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The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Tool Suite Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 2 The University of Edinburgh, Scotland Joint work with Federica Ciocchetta, Adam

  1. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Tool Suite Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 2 The University of Edinburgh, Scotland Joint work with Federica Ciocchetta, Adam Duguid, Stephen Gilmore and Maria Luisa Guerriero Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 3 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  2. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Introduction Bio-PEPA is a timed process algebra designed specifically for the description of biological phenomena and their analysis through quantitative methods such as stochastic simulation and probabilistic model-checking. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 4 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  3. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Context The context of application we consider is that of biochemical networks. ◮ A biochemical network is composed of N species which interact through M reactions; ◮ the dynamics of reaction j is described by a kinetic law. ◮ The quantitative behaviour of a biochemical network depends on the initial values of the involved species and on the kinetic parameters. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 5 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  4. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  5. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  6. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  7. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  8. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  9. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Model component P ::= P ⊲ ⊳ L P | S ( l ) Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  10. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Model component P ::= P ⊲ ⊳ L P | S ( l ) Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  11. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Model component P ::= P ⊲ ⊳ L P | S ( l ) Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  12. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Model component P ::= P ⊲ ⊳ L P | S ( l ) The parameter l is abstract, recording quantitative information about the species. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 6 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  13. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA languge Sequential component (species component) S ::= ( α, κ ) op S | S + S | C where op = ↓ | ↑ | ⊕ | ⊖ | ⊙ Model component P ::= P ⊲ ⊳ L P | S ( l ) The parameter l is abstract, recording quantitative information about the species. Depending on the interpretation, this quantity may be: ◮ number of molecules (SSA), ◮ concentration (ODE) or ◮ a level within a semi-quantitative model (CTMC). Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 7 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  14. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Software Tools Two software tools are available for modelling with Bio-PEPA, ◮ the Bio-PEPA Workbench, and ◮ the Bio-PEPA Eclipse Plugin. Both modelling tools allow the user to analyse their model both in the discrete stochastic regime and in the deterministic continuous regime while maintaining only a single source in the Bio-PEPA language. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 8 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  15. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Workbench Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 9 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  16. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Stochastic simulation With respect to stochastic simulation, the Bio-PEPA Workbench generates the kinetic laws and propensity function descriptions which are needed to perform an analysis of the model via stochastic simulation using Gillespie’s Stochastic Simulation Algorithm (SSA) and other stochastic simulation algorithms such as Gibson-Bruck. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 10 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  17. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Model-checking As an alternative to simulation, the Bio-PEPA Workbench can also generate a CTMC model in the format accepted by the PRISM model-checker together with a reward structure and typical formulae of CSL logic which can be checked against the PRISM model. Each species component gives rise to one PRISM module. Custom rate expressions are generated to ensure that the generated PRISM model correctly reflects the dynamic behaviour of the input Bio-PEPA model. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 11 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  18. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Continuous simulation For continuous simulation, the Bio-PEPA Workbench generates the reaction rate equations in the form of a system of coupled ODEs. The system variables of the ODEs allow us to determine the quantity of each chemical species in the reaction at any point up to a finite time horizon, and in the long run. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 12 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  19. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plug-in is a rich modelling environment for Bio-PEPA which aims to provide strong support for investigating the average case dynamic behaviour of systems. Users can compare stochastic ensembles of independent simulation runs with the mean trajectory obtained by generating the differential equation model and numerically integrating this. Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 13 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  20. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plugin Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 14 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  21. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plugin Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 15 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  22. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plugin Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 16 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  23. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in The Bio-PEPA Eclipse Plugin Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 17 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

  24. The Bio-PEPA Workbench The Bio-PEPA Eclipse Plug-in Example results Jane Hillston School of Informatics and Centre for Systems Biology at Edinburgh 18 The University of Edinburgh, Scotland The Bio-PEPA Tool Suite

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