Copasi

Introduction

Copasi is an open source software package for modeling and simulation of biochemical reaction networks. Copasi can import and export SBML (Systems Biology Markup Language), which is a file format for exchanging models with other systems biology software.

Model Creation

1. Click the "Model" tab from the side of the home page.
2. Rename the model.
3. Adjust the units according to your needs.
4. Write any comments in the large text box
5. Choose the biochemical tab from the side underneath the "Model" tab. Choose "Compartment" from the drop down list.
6. Rename the compartment and and double click on the compartment.
7. Once the compartment is adjusted to your needs, click on the "Reactions" tab.
8. Double-Click the reaction to rename and then double-click the reaction again to put in the chemical equation. Using the equal sign means the reaction is reversible. -> means the reaction is irreversible.
9. Press the new button to create a new reaction.
10. Adjust rate law according to your needs.
11. If the rate law you need is not in the list, select the "New Rate Law" button.
12. Enter the mathematical formula into the "Formula" box.
13. Press the "Commit" button when finished with the rate law.
14. Click the "Reactions" tab to see a summary of the information you have entered.
15. Select the "Species" tab to see all of the species.
16. Double-click on a species to edit the simulation type, initial concentration, rate and reactions for that species.
17. Select "Parameter of Review" from the side tabs to review all of the information.
18. Select the "File" tab to save the model.

Time Course Simulation

A model must be created before creating a time course simulation.

1. Select the "File" tab and then click "file" to load a model.
2. Select the triangle next to "Tasks" to expand the drop-down menu.
3. Select "Time Course" then hit "Run."
4. Select "Result" from the "Time Course" drop-down to see a table of the data. Select "Save" to create a txt file for the data.

To get a plot...

1. Select the "Output Assistant" button on the the "Time Course" page.
2. Select the pre-designed plot value and click "Create."
3. Check the "Active" box to make sure the plot appears next time the program is run.
4. Click "Time Course" then "Run" to see the plot.

Duration

• Setting the duration to suppress before a certain time gives the simulation "time to settle in."
• Larger intervals speed up the run.

Basic Plotting

A model must be created before creating a plot.

1. Load a model.
2. Run a Time Course of the model.
3. Select "Output Assistant."
4. Select the type of plot desired and press "Create."
5. Click "Run."

Phase Space Diagram

Diagram of one variable vs. the other where time is no longer explicit.

1. Click the "Output Specifications" tab.
2. Select "Plots" from the drop down menu.
3. Rename the plot and select "New Curve."
4. Define the X axis as a "Transient Concentration" of one of the species.
5. Define the Y axis as a "Transient Concentration" of the other species.
6. Change the title of the curve and press "Commit."
7. Run a time course of the model.

Histogram

1. Click the "Output Specifications" tab.
2. Select "Plots" from the drop down menu.
3. Rename the plot and select "New Histogram."
4. Choose the variable from "Species" --> "Transient Concentrations."
5. Choose the increment or "bin size."
6. Change the title of the histogram and press "Commit."
7. Run a time course of the model.

Steady State

Steady state is a condition in which all of the concentrations do no change with time. This happens when all of the reaction rates consuming the species are in balance with the rates producing them. Copasi uses the Newton method, integration, and backwards integration for steady state reactions.

1. Click the "File" tab then select "Examples..." from the drop-down menu.
2. Choose "COPASI files" and select the "MAPK..." file from this folder.
3. Click the triangle next to "Task" then select "Steady State."
4. Adjust the methods and click "Run."
5. Click the triangle next to "Steady State" to reveal the "Result" tab. Click that tab to see the results window.
6. Click the "Stability" tab to see if the conditions were stable.

Finding a combination of methods that works may take some trial and error. You can check your steady state by making a plot and ensuring the lines are all completely horizontal.

Figure 1. This graphic depicts the difference between a stable and unstable steady state. While both of these are steady states, only one is stable.

Reports

How to configure output text reports.

1. Load a model
2. Set up a task
3. Click "Output Assistant" and choose an option under "Reports."
4. Click the triangle next to "Output Specifications" then choose "Report Templates" your new template should have appeared.
5. Customize the template by deleting the parameters you are uninterested in.
6. Return to your task and click the "Report" button.
7. Select your report template, uncheck the "Append" box, rename the file, and click "OK."
8. Run the task.
9. Click "Yes" to the pop-up window.

Opening the file in a spreadsheet software

• Separate by tabs.

Parameter Scanning and Sampling

1. Click the triangle next to "Tasks" and select "Parameter Scan" from the drop down menu.
2. Choose the calculation you want to perform from the drop down menu.
3. Click the "Create" button to create a new scan item.
4. Select desired parameters from the drop down menus and click "OK."
5. Create a plot of the reaction fluxes
6. Click "Output Specifications" then click "Scan of reaction fluxes" and edit the curve specifications to only show the desired fluxes.
7. Return to the "Task" page and click "Run" to run the scan.

Metabolic Control Analysis

Metabolic Control Analysis (MCA) is a mathematical framework used to assess how the control upon the steady state values of the system's variables is distributed among the different reactions.

Calculating Control Coefficients

1. Download the model on which you wish to run an MCA.
2. Click the triangle next to "Task" and select "Metabolic Control Analysis" then click "Run."
3. Select the Flux Control Coefficients Tab.

Flux Control Coefficients Tab

• Rows represent the fluxes of the reactions.
• Columns represent the enzymes that catalyze the reactions.
• Flux control coefficients can be negative.

Concentration Control Coefficients

• Columns represent the perturb of the enzymes.
• Rows represent the species that were affected.

Helpful Tips

• If a box is highlighted pink in copasi, there is an error with that information.
• Make sure the duration is long enough for the plot to oscillate if the plot is oscillating.
• For Steady-State, if you only want to use one method, the other methods can be set to 0.
• If the rates are not close to zero in the results of the steady state, then you need to adjust the method.
• You can change the order in which parameter scans are run.

References

Copasi Website