VCell. vcell.org. To run VCell go to: modeling environment for mathematical simulation of cellular events.

Transcription

1 VCell modeling environment for mathematical simulation of cellular events. To run VCell go to: vcell.org Virtual Cell is developed by the Center for Cell Analysis and Modeling at the University of Connecticut Health Center. It is funded as a Biomedical Technology Research Resource by the National Institute of General Medical Sciences (NIGMS)

2 VCell Tutorial BioModel with Multiple Applications Create a single biomodel of RAN nuclear transport then use different modeling strategies to solve simulations.

3 The Multi-App Tutorial Part 1: Spatial Deterministic Application using a 3D geometry derived from an image stack Create the Physiology for a simple Biomodel of RAN nuclear transport, create a 3D geometry directly from a z-stack of microscopy images, and run a deterministic spatial simulation. Part 2: Additional Applications Compartmental stochastic application with data export; compartmental deterministic (ODE) application with parameter estimation parameters using external data; stochastic spatial application.

4 In this tutorial Create a Biomodel Physiology with species, reactions and fluxes Create a spatial deterministic application of the Physiology Import a fluorescence images into Vcell and segment a 3D image stack within VCell to create a geometry Create a simulation and specify solver, time, and computational mesh. Run the simulation, view results and create graphs

5 Table of contents Re-Open a model Copy an application Create a stochastic simulation Export results as spreadsheet Create a non-spatial deterministic application Using parameter estimation Create a spatial stochastic application

6 To re-open a model, click on the folder that the model was saved in and double-click on the model.

7 You can create a new application by making a copy of an existing applications. To create a non-spatial stochastic copy of the existing application, right click on an application and click Copy As > Non- Spatial > Stochastic.

8 Click OK.

9 To rename an application, right click on the application, click Rename, type in a name, and press Enter on your keyboard.

10 To create a new simulation, click Simulations and the new simulation icon.

11 To edit the simulation, click the edit simulation icon.

12 To edit the solver for a simulation, click the Solver tab, type in values, and click OK.

13 Click the green play icon to run the simulation.

14 To view simulation results, select the simulation and click the results icon.

15 Change Display Options to show only species variables To view a spreadsheet of the simulation results, click the spreadsheet icon.

16 For this tutorial, select the RanC_cyt species data to display. To copy the spreadsheet, right click on a cell and click Copy All.

17 Open your favorite spreadsheet software, click on an empty cell, and paste the simulation results for RanC in the cytosol. We will use this data later to demonstrate parameter estimation tools.

18 Save the spreadsheet as a comma delimited format.

19 Click OK

20 Click Yes. The NonSpatial Stochastic application is now complete.

21 To create a non-spatial deterministic copy of an application, right click on an application and click Copy As > Non-Spatial > Deterministic.

22 To rename the new application, right click on an application and click Rename. Type in a name and press Enter on your keyboard.

23 When you copy a spatial application to a non-spatial application, VCell automatically uses sizes for the compartments based on the image-based geometry used in the spatial application The NonSpatial Deterministic Application therefore is all ready to run simulations. In this tutorial, we will first use data to fit one of the parameters for the model

24 To create a new parameter estimation, click Parameter Estimation tab and click the plus sign icon.

25 To select a parameter to fit, click on the specific parameter, in this case Kf, and click OK.

26 Continue adding parameters until you have using the plus sign icon until you have selected all the parameters you want to fit.

27 To import experimental data, use the Experimental Data Import tab, then Import from CSV file.

28 To select experimental data to import, click the desired CSV file and click Open.

29 To map a concentration, click Experimental Data Mapping > an unmapped concentration > Map Experimental Data

30 To select which concentration to map, click on the desired species and click OK.

31 To solve for parameter estimations, click Run Task > Solve by Copasi.

32 Notice how accurate the estimate is in relation to the model value To plot estimation values versus model values, click Plot.

33 To compare estimation values to model values, compare the fit of their lines and click Close when done.

34 Now we will create a spatial stochastic application. Right click on the Spatial Deterministic application and click Copy As > Spatial > Stochastic.

35 Right click the application and press Rename to type in a new name. Press Enter on your keyboard.

36 To work with number of particles instead of concentration (for stochastic models only), double click your new application and click Specifications > Number of Particles.

37 To change the number of particles of a species, type in a value under the Initial Condition column.

38 To create a new simulation, click Simulations and the new simulation icon.

39 To edit a simulation, click the simulation and click on the edit simulation icon.

40 To edit the mesh of a simulation, click the Mesh tab and type in desired values.

41 To edit the solver of a simulation, click the Solver tab and type in values. Click OK.

42 To run and save a simulation, click the green play icon.

43 To view simulation results, click the simulation and click the results icon.

44 To change the image being viewed, hold down and drag using the Z- slicer.

45 To change the time frame being viewed, type in a value under Time or hold down and drag the slider under Time. Your model is now complete!