CompuCell SoftwareCompuCell Software

Current capabilities and Research Plan

Rajiv ChaturvediJesús A. Izaguirre

With Patrick M. Virtue

ObjectiveObjectiveIntroduction to integrated Potts model simulation and visualization package called CompuCellShow simulation results (application to macrophage and bacteria movement)Present a Research and Development plan to

Model chicken limb growthModel Integration (Potts and Reaction Diffusion)

Talk OutlineTalk OutlinePreliminary results:

Current model and software capabilities Macrophage simulation results

Research and Development plan Modeling

Cell condensation in 2D Chicken limb bud in 2D R-D integration (Flock modeling)

Software Integration of other models (eg., Reaction Diffusion) GUI designed for generality 3-d simulation an dvisualization

Movie from experimentsMovie from experimentshttp://www.nd.edu/~icsb

Problem schematicProblem schematicMacrophage 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

Results: Model DescriptionResults: Model DescriptionHamiltonians:

VolumeSurfaceInteractionChemotaxis

Multiple gradients of chemical fieldLinearRadial distribution of concentration from a source

Field implementationCurrent limitation: Field as action at a distance rather than diffusing through lattice

Results:Results: Initial and boundary Initial and boundary conditionsconditions

SubDomains in software <-> Cells in the model: Experimented with 2 and 3 cells in the lattice

Boundaries: The pixels of the changing bacteria boundary act as sourcePeriodic boundary conditions on lattice edges

Results: Verification and Results: Verification and validationvalidation

Verification: Potts model for multiple fluctuating cells without chemotaxis HamiltonianPotts model for moving cells with linear gradient

Validation Qualitative studies (visual inspection) for patterns formed and those observed

(Show animated gif)

Results: SoftwareResults: Software

Software: Interactive (integrated with visualization)Stand-alone

Visualization: Uses VTK (visualization tool kit) libraries Movie creation capabilitiesImage manipulation: rotate, zoom, sectionVisualization done by Patrick Virtue

Results: GUIResults: GUI Allows user to define initial conditions

Cells of arbitrary shape on a lattice Visualization properties for cells

Future integration with CompuCell discussed below

Results: GuiResults: GuiGUI:

Results: VisualizationResults: VisualizationVisualization 3D hydra burst:

Results: Software Results: Software extensibilityextensibility

Object Oriented design: caters for reuse and extensibility by

Hierarchy of classes: General to specificAbstractionEncapsulation

Computational engines running multiscale simulations (ellipses)

Potts Reaction diffusion

Data Communication

Experimental data

Computational engine running Analysis

Visualization Engine

High Level Architecture for Integrated PSE

GUI

Results: Software Results: Software extensibilityextensibility

Addition of new hamiltonians (at programming level):

Derive new hamiltonian from abstract Hamiltonian classEncapsulate its data, mimic methods of other HamiltoniansTotal Hamiltonian (a subclass of Hamiltonian) takes care of Energy calculationsIn modeling code, create objects of various types of Hamiltonians, add them to TotalHamiltonian object

Addition of new fields: similarAddition of new boundary conditions

Results: SoftwareResults: Software

Input: Command line

prompts File input (and from

GUI) Initial conditions

Lattice Cells

Positions and sizes

Parameters Constraints

params…

Output: Runtime

visualization Movies Post processing

mode

Results: cell movement in Results: cell movement in gradient gradient

(Show animated gif)

Talk OutlineTalk OutlineOverview: Integrated Problem Solving EnvironmentPreliminary results: bacteriophage problem

Current model and software capabilitiesBacteriophage simulation results

Research and Development planModeling

Steps to Chicken limb bud R-D integration

Software Integration of other models (eg., Reaction Diffusion) GUI designed for generality Visualization

Research Plan: Cell SortingResearch Plan: Cell SortingProblem 0: (Cell sorting in the presence of a gradient)

Research Plan: CondensationResearch Plan: CondensationProblem 1: (Cell condensation in the presence of reaction-diffusion)

Research Plan: Limb bud Research Plan: Limb bud growthgrowth

Problem 2:

Full of 3D cells No activity in

Progress zone

TimeProgress Zone

Research Plan: Limb bud Research Plan: Limb bud growthgrowth

Problem 1 and 2:

K steps of Reaction Diffusion in a lattice

Potts model movement, cells as moving sources

R&D plan: Limb bud R&D plan: Limb bud growthgrowth

Model extension needed: Diffusive gradients Reaction diffusion equations to solve Extra cellular matrix characterization (field) Progress zone characterization (in Potts model) Set of reasonable initial/boundary conditions, and parameters for Potts model validation 3 D potts 3 D RD

R&D plan: Limb bud R&D plan: Limb bud growthgrowth

Software Extension needed/desired: Front end:

Integration and extension of GUIAutomated tuning of parameters (software detects param ranges where desired behavior is obtained)

Computational backend:Integration with reaction-diffusion code Handling multiple grids (hierarchy of grids, interpolation)Clustering algorithms to detect pattern formationMore efficient solvers (for 3D)

Issue of accuracyIssue of accuracyA working definition of “good” simulation for various simulations needs to be defined.

Verification: Solving the model rightVerification against known analytical solutions

(analytical results for statistical variables in stochastic models)Quantifying accuracy of results against grid size

Validation: Solving the right model: basis of comparing results to experiments

Integrated Problem Solving EnvironmentIntegrated Problem Solving Environment

Grand aim: The end user must be able to focus on Biology/ Physics problems rather than software/ programming. Runtime and post processing visualizationConfiguration files to specify initial conditions and simulation parametersRecommender system (to assist user)GUI to allow for user inputsAbility to allow user to choose models (in the long run) through a GUI