1. CompuCell Software Current capabilities and Research Plan Rajiv Chaturvedi Jesús A. Izaguirre With Patrick M. Virtue

2. Objective u Introduction to integrated Potts model simulation and visualization package called CompuCell u Show simulation results (application to macrophage and bacteria movement) u Present a Research and Development plan to n Model chicken limb growth n Model Integration (Potts and Reaction Diffusion)

3. Talk Outline u Preliminary results: n Current model and software capabilities n Macrophage simulation results u Research and Development plan n Modeling l Cell condensation in 2D l Chicken limb bud in 2D l R-D integration l (Flock modeling) n Software l Integration of other models (eg., Reaction Diffusion) l GUI designed for generality l 3-d simulation an dvisualization

4. Movie from experiments http://www.nd.edu/~icsb

5. Problem schematic Macrophage and bacterium wbc bacterium Periodic boundary conditions on square lattice Gradient fields in medium Linear field from left to right Radial field originating from bacteria Update field after each move

6. Results: Model Description u Hamiltonians: n Volume n Surface n Interaction n Chemotaxis u Multiple gradients of chemical field n Linear n Radial distribution of concentration from a source u Field implementation n Current limitation: Field as action at a distance rather than diffusing through lattice

7. Results: Initial and boundary conditions u SubDomains in software Cells in the model: n Experimented with 2 and 3 cells in the lattice u Boundaries: n The pixels of the changing bacteria boundary act as source n Periodic boundary conditions on lattice edges

8. Results: Verification and validation u Verification: n Potts model for multiple fluctuating cells without chemotaxis Hamiltonian n Potts model for moving cells with linear gradient u Validation n Qualitative studies (visual inspection) for patterns formed and those observed

9. (Show animated gif)

10. Results: Software u Software: n Interactive (integrated with visualization) n Stand-alone u Visualization: n Uses VTK (visualization tool kit) libraries n Movie creation capabilities n Image manipulation: rotate, zoom, section n Visualization done by Patrick Virtue

11. Results: GUI u Allows user to define initial conditions n Cells of arbitrary shape on a lattice n Visualization properties for cells u Future integration with CompuCell discussed below

12. Results: Gui u GUI:

13. Results: Visualization u Visualization 3D hydra burst:

14. Results: Software extensibility u Object Oriented design: caters for reuse and extensibility by n Hierarchy of classes: General to specific n Abstraction n Encapsulation

15. Computational engines running multiscale simulations (ellipses) PottsReaction diffusion Data Communication Experimen tal data Computational engine running Analysis Visualization Engine High Level Architecture for Integrated PSE GUI

16. Results: Software extensibility u Addition of new hamiltonians (at programming level): n Derive new hamiltonian from abstract Hamiltonian class n Encapsulate its data, mimic methods of other Hamiltonians n Total Hamiltonian (a subclass of Hamiltonian) takes care of Energy calculations n In modeling code, create objects of various types of Hamiltonians, add them to TotalHamiltonian object u Addition of new fields: similar u Addition of new boundary conditions

17. Results: Software u Input: n Command line prompts n File input (and from GUI) n Initial conditions l Lattice l Cells u Positions and sizes n Parameters l Constraints params… u Output: n Runtime visualization n Movies n Post processing mode

18. Results: cell movement in gradient (Show animated gif)

19. Talk Outline u Overview: Integrated Problem Solving Environment u Preliminary results: bacteriophage problem n Current model and software capabilities n Bacteriophage simulation results u Research and Development plan n Modeling l Steps to Chicken limb bud l R-D integration n Software l Integration of other models (eg., Reaction Diffusion) l GUI designed for generality l Visualization

20. Research Plan: Cell Sorting u Problem 0: (Cell sorting in the presence of a gradient)

21. Research Plan: Condensation u Problem 1: (Cell condensation in the presence of reaction-diffusion)

22. Research Plan: Limb bud growth u Problem 2: Full of 3D cells No activity in Progress zone Time Progress Zone

23. Research Plan: Limb bud growth u Problem 1 and 2: K steps of Reaction Diffusion in a lattice Potts model movement, cells as moving sources

24. R&D plan: Limb bud growth u Model extension needed: l Diffusive gradients l Reaction diffusion equations to solve l Extra cellular matrix characterization (field) l Progress zone characterization (in Potts model) l Set of reasonable initial/boundary conditions, and parameters for Potts model validation l 3 D potts l 3 D RD

25. R&D plan: Limb bud growth u Software Extension needed/desired: l Front end: u Integration and extension of GUI u Automated tuning of parameters (software detects param ranges where desired behavior is obtained) l Computational backend: u Integration with reaction-diffusion code u Handling multiple grids (hierarchy of grids, interpolation) u Clustering algorithms to detect pattern formation u More efficient solvers (for 3D)

26. Issue of accuracy u A working definition of “good” simulation for various simulations needs to be defined. n Verification: Solving the model right l Verification against known analytical solutions u (analytical results for statistical variables in stochastic models) l Quantifying accuracy of results against grid size n Validation: Solving the right model: basis of comparing results to experiments

27. Integrated Problem Solving Environment u Grand aim: The end user must be able to focus on Biology/ Physics problems rather than software/ programming. u Runtime and post processing visualization u Configuration files to specify initial conditions and simulation parameters u Recommender system (to assist user) u GUI to allow for user inputs u Ability to allow user to choose models (in the long run) through a GUI