TiSim - Modelling and Simulation Software for Lattice-Free Agent-Based Biophysical Tissue Models.

Welcome to the TiSim preview.

This is a short introduction into how you can use this application and to explore the supplied examples. This is by no means intended to be a complete documentation, which will come with the release. It is also not meant as an overview of the full capabilities of TiSim, from which some were indicated by the previous page.

Please download a preview version of TiSim for Windows (~ 70MB) (updated [2020-06-16 00:43]). Download can take up to several minutes depending on the internet connection.

Before you proceed, please take a look at the Quick Start section in this short TiSim README.

   

Starting the application

Just double-click the TiSim.exe in the extracted TiSim-Preview folder. Please do not move the executable, qt.conf, or the subfolders (data and dlls), to ensure the application runs as expected. You may rename and move the enclosing TiSim-Preview folder.

The Wizard

After clicking the TiSim executable, you will be greeted by the TiSim Wizard, which lets you choose on of the examples we present with the application. Use the combo box (see image) to select an example. Click ‘Continue’ to start the example.

 

The Application Window

A new window will open up. This is the main application window, which is subdivided in the model interaction bar on the bottom of the window, and several tabs, that each have their special purposes.

 

The Model Interaction Bar

The region at the bottom of the main application window serves as the centre for interacting with the model.

 

It features, from left to right, buttons to a) initialize, abort, or reset the model, b) start and pause the simulation. The progress bar above the buttons will show the temporal advancement of the simulation, or show that the application is busy (e.g. with an initialization process).

Following are two fields to specify the start time and end time of the simulation. Mind, that the start time has no influence on the starting configuration, the time simulated is the difference of end and start time. The start time is only to clarify that the system started already some time after experimental setup. You may increase the end time to extend the simulation.

The last field on the right will determine the update frequency of data output. This will be shown on the ‘Output’ tab, see below.

The Visualization Tab

As the name tells it, this is where the visual representation of the models are displayed. You will be able to rotate and zoom the scene and view the simulation progress in real-time.

To choose different virtual tissue staining, choose the menu “View Options” at the top of the main window and select “Cell Staining…”. A side part of the Visualization area will show, in which you can choose the observable to visualize. The scale of the values ranges from lowest values as green to highest values in red. A legend for these values will be provided in the release version.

To hide the visualization options, open the “View Options” menu and click on “Cell Staining…” again.

 

The Parameters Tab

Parameters are an important part of the model. Each model example only exposes a selected few parameters that are meaningful to vary. Here you can choose values from the literature, or vary them in any way suitable for you to explore the behaviour of the tissue under different conditions.

A short warning: The application might still crash when parameter values are outside the well-behaved domain.

To change a parameter value, double-click the value field, or toggle the tick mark.

  • For numerical values, just enter the value.
  • Choices offer a menu to choose from.
  • In the case of file or directory paths, there will be a button, marked ‘…’ on the right end of the input field. Pushing this button will open a file browser with which you can navigate to the desired path. If, after a finished edit, the field is displayed in red, it means, the path could not be found!
  • Tick marks toggle on single click.

The Output Tab

This tab features a table of pre-selected global observables. When run, the data describe the time-course, with the model time in the column at the left end. You may want to save the data to CSV - a format readable by MS Excel and other spreadsheet-based calculation programs like LibreOffice and WPS. To do so, click the button on top of the table, marked “Save to CSV (Excel readable)”.

 

The About Tab

Here you can find the current version number and the list of developers which substantially contributed to the TiSim application and models, both in basic theory, modelling and coding, to varying degrees.

Quick Start

  1. After downloading the zip file, open it via the browser or double-click the zip-file in the Finder.
  2. Extract the content to a folder of your choice (E.g. C:\Users\yourName\Desktop\TiSim-Preview).
  3. Open that folder and double-click TiSim.exe. A window will open, where you can choose an example of interest.
  4. Having chosen, push the ‘Continue…’ button, and the main TiSim Window will open (see above for more details).
 

In the main window, you can directly push the initialization button on the lower left corner, and subsequently the run button to the right of it.

At any time after initialization, you can change, by what quantity to color the cells. To do that, open the “View Options” menu at the top of the window and choose “Cell Staining…”. In the side window on the “Visualization” tab, you can pick a color an observable. For any of these settings you can also regulate transparency with the slide bar.

 

A run can be interrupted (paused) by pushing the pause button, or aborted by pushing the stop button. After this, the simulation can be reset by pushing the initialization button (which was the stop button during simulation).

When run, the simulation produces data. Most prominently researchers are interested in global observables, i.e. quantities calculated over the whole system or over one of the cell populations, like number of cells and population radius. For easy access to these data, TiSim’s GUI features the Observables tab, on which a set of selected global variables are recorded in a table. This data is updated in real-time from the simulation loop. It can be written to a so-called CSV-file (for Comma-Separated Values), which can be imported to MS Excel or LibreOffice Calc.

 

Examples

All examples are available in the wizard. After finishing the wizard, you can initialize and start the simulation directly. The provided default parameters are already set to values as used in the publication. To reproduce other parameter settings given in the paper, choose the “Parameters” tab and change the corresponding parameter by clicking (in case of tick marks) or double-clicking and specifying a value (numerical and path variables) or, in the case of choices, double-clicking, clicking again to open the options and choosing the corresponding option (e.g. “Contact Model”, “Cell Cycle Inhibition Mechanism”).

Center-based Tumor Spheroid Growth

 

Tumor Growth in Embedding Medium (2D, Center-Based)

 

TRAIL Resistance Model with Center-Based Monolayer

 

Liver Lobule Regeneration

Rem.: The view of the simulation is a time lapse of the regeneration process. The full simulation may take up to three days, depending on your computer’s performance.

 

DCM Tumor Spheroid Demonstration

 

Major contributions to this software have been made by:
Andreas Buttenschon, Géraldine Cellière, Dirk Drasdo[1], Daniel Hahne, Stefan Hoehme, Tim Johann[2], Paul Van Liedekerke, Johannes Neitsch, Jieling Zhao.

[1]: Principal Investigator.
[2]: Contact: johann@ifado.de

Tim Johann, Last change [2020-06-24 Wed]