This document provides instructions for performing kinetic simulations using the GeneXplain platform. It describes registering for an account, logging in, selecting the BioModels database to access publicly available models, searching for and selecting the Tiemann et al (2011) lipoprotein metabolism model, running a simulation of the model, interpreting the output, plotting different variables, changing parameters, comparing simulations, and changing to a different model. The overall purpose is to demonstrate how to set up and run kinetic simulations of biological models using the online GeneXplain platform.

1. Performing kinetic simulations
using the GeneXplain platform
Manual

2. Before you start
Have your (SBML) model ready. In these
demonstrations, we will use models publicly available
at the BioModels database – which will be directly
accessible from the GeneXplain platform.
(http://www.ebi.ac.uk/biomodels-main/)

3. Lipoprotein metabolism – Tiemann et al (2011)
The model we will use in this tutorial is found in the Biomodels
database – Tiemann2011_PhenotypeTransitions

4. Lipoprotein metabolism – Tiemann et al (2011)
This model describes
lipoprotein
production, remodelling and
uptake.
It is an ODE (ordinary
differential equation)
model, based on mass-action
kinetics.
(For more information on ODE
models, please see
cbio.bmt.tue.nl/resolve )

5. Lipoprotein metabolism – Tiemann et al (2011)
The model contains 11 states
Plasma
•
TG (Triglycerides) in VLDL/IDL/LDL
•
CE (Cholesteryl ester) in VLDL/IDL/LDL
•
CE (Cholesteryl ester) in HDL
Liver
•
TG (Triglycerides)
– cytoplasm
•
CE (Cholesteryl ester)
– cytoplasm
•
TG (Triglycerides)
– endoplasmatic reticulum
•
CE (cholesteryl ester)
– endoplasmatic reticulum
•
FC (Free cholesterol)

6. For more information on the model
Please see:
‘cbio.bmt.tue.nl/resolve/model_development/human_models’
•
Christian A.Tiemann, Joep Vanlier, Peter A.J. Hilbers and Natal A.W. van Riel.
Parameter adaptations during phenotype transitions in progressive diseases
BMC Systems Biology 2011, 5:174 doi:10.1186/1752-0509-5-174
•
Christian A.Tiemann, Joep Vanlier, Maaike H. Oosterveer, Albert K. Groen, Peter A.J.
Hilbers, Natal A.W. van Riel. Parameter Trajectory Analysis to Identify Treatment
Effects of Pharmacological Interventions
PLoS Comput Biol 9(8): e1003166. doi:10.1371/journal.pcbi.1003166

7. 1. Register
To simulate on the GeneXplain platform, you
must be in possession of a valid account for the
GeneXplain platform.
You can register at:
http://genexplain.com/genexplain-platform-1
(If you are a member of RESOLVE, your trial account can be
converted to a full account).

8. 2. Log in
Log in using the e-mailaddress and password of your GeneXplain account.
(Lost passwords can be reset – send an e-mail to info@genexplain.com)

9. 2. Log in

10. 3. Select 'Databases’
The databases tab is found at the top left of your screen.

11. 3. Select 'Databases’
The databases tab is found at the top left of your screen.

12. 4. Select 'BioModels’
Select the BioModels database to access models archived in the BioModels
database – like Tiemann et al (2011)

13. 4. Select 'BioModels’

14. 5. Search for a specific model
Start typing the BioModels name of your model you
looked up earlier. In this case, start typing
“tiemann2011…” and the correct model will be
suggested.

15. 5. Select the suggested model entry and
click on the binocular
A model matching your query is shown –
select it and press “search” again. The model
should now appear in the white field at the
bottom right of your screen.

16. 5. Select the suggested model entry and
click on the binocular

17. 6. Select model
Click on the underlined model name (number in BioModels Database)

18. 6. Select model
Click on the underlined model name (number in BioModels Database)

19. 6. Model overview
In the drop-down menu at the top of the left lower panel, you can choose
how to visualise the model, e.g. with ordinary differential equations.
Biochemically-based models may be well-visualized by choosing “reactions” choosing this for the Tiemann model should yield this result:

20. 6. Model overview
While more phenomenological models which are governed by “rules”
may be better viewed via “Overview”.

21. 7. Click on the tab 'Simulation‘ (right lower panel)

22. 7. Click on the tab 'Simulation‘ (right lower panel)

23. 8. Run the simulation
Click on the 'play' button

24. 9. Output
You obtain a separate window with the simulation results of all the
species that are incorporated in the chosen model

25. 10. Interpreting the output
The plot produced by the simulation
contains the values of all states over
time.
In this case, we can see the
lipoprotein model departing from its
initial state and reaching a
steady state.

26. 11. Plotting the variables you are interested in
You can change the variables plotted by visiting the “Variables”
and “Parameters” tabs – found next to the “simulation” tab.

27. 11. Plotting the variables you are interested in
By ticking the boxes under “show in plot” you
can determine which values you would like to
see plotted over time.
Note that these boxes appear under both
“Variables” and “Parameters”, and all will be
plotted in the same figure.

28. 12. Changing the parameters of your model
The values of initial conditions (i.e., the concentration at the
beginning of your simulation) can be changed under “Variables”.
Initial conditions
Note that some “variables” are
constants, here the liver and
plasma volumes and
FFA concentration

29. 12. Changing the parameters of your model
The values of model parameters can be changes under
“parameters”.
Parameters that determine model
behaviour are constant.
The value of a parameter can be changed
by entering a new value in the box.

30. 13. Comparing simulations
If you leave the old plot screen “open” and simulate again with the new
parameters, they can be compared.
Note that you must return to the “Simulations” tab to be able to run the simulation.
Here, we have changed the value of reaction_10_v from 1.30725E-5 to 1.0 for a
demonstration.
reaction_v_10 = 1.30725E-5
reaction_v_10 = 1.0

31. 13. Comparing simulations
The behaviour of the model should change as shown below
• This is not a phsyiologically relevant change, simply an example of changing a
parameter value.
• The colors and (order of the) legend in your simulation may not match the colors
and legends shown below.
reaction_v_10 = 1.30725E-5
reaction_v_10 = 1.0

32. 14. Changing the model you are working with
To change the model you are working
with, again click on the BioModels database and
select a model as previously explained.

33. This concludes the short introduction to webbased simulation using the GeneXplain platform.
Please continue with:
- Web based simulations of Murine Lipoprotein Metabolism
- Web based simulations of the Postprandial Glucose Response

34. cbio.bmt.tue.nl/resolve