Problems with SimBiology analysis of BioModels files.

I am trying to simulate on SimBiology basic human cellular respiration, and see how changing the concetration of input species can yield different graphs. I tried BioModels and a lot of the files that were about respiration contained errors when imported and run. What can I do when those files which interest me are full of errors? I realised too a lot of them came from KEGG.

Within the curated files, I downloaded Chance_1960_Glycolysis_Respiration and it was runnable. But its specis had no units for concetration. I changed all the nonzero concentration species into mM units, and changed glucose to 5 mM. I am just trying to model cell respiration from a cell culture in a well, nothing to complex. It turns out the graph plotted nothing, it stayed constant at 0 and all the curves from the original file were gone. It doesn't seem to be simulating it right.

Among the curated models, I can't find many files of my interest, related to oxidative phosphorylation or extracellular matrix biosynthesis, as I find among the rest of the database, but which contain errors.

Could you help me, please? Thank you very much! This is very time-sensitive.

Answer 1

[Rick Paxson]

Hi - Unfortunately it is often the case that models have no units specified. You might be able to figure out what the units are by looking at the model description on BioModels. The assumption I would make is that the authors have written the model using values that are consistent dimensionally and with the correct units.

To make sure we are seeing the same thing. I downloaded the file you mention and ran it. I get the following simulation results.

The model is setup with an initial value of Glucose of 0 and then increases to .003 at time 64 (i.e. the amount of Glucose is controlled by an Event that triggers at time == 64. You can see this in the Model Browser:

To change the amount of Glucose you would change the value here shown as 0.3 (I changed it from .003 to 0.3). Note that the simulation stop time is set to the default value of 10 so glucose is set to 0 in this time window. To change the stoptime open the "simulation settings" in the Task editor toolstrip and change the stop time to, say, 100. Ignore the TimeUnits as the model has no units in it.

There are many states in this model so you may want to right click on the plot and using the Properties dialog select the states you want to plot. Here is an example showing only Glucose:

Note that at time = 64 Glucose jumps from 0 to .3.

Here are a few other states:

Hope this is helpful.

[Juan Carlos Cao Yao]

Thank you Ricardo! That was some detailed answer. I got it working like you.

Answer 2

[Juan Carlos Cao Yao]

Hi Ricardo, I have some more troubles with this model. I have set the glucose's trigger concentration to 0.3 like you. When I run it for 1000 s, I get the step increase of glucose and mildly decreases in time, while oxygen, lactate or pyruvate stay at near 0 levels:

When I run it for 3600 s, I get an error, while the graph remains the same:

Conversely, when I run it for 1 hour which is the equivalent, results are different.

When I run it for 2 days, the step increase in glucose that was seen in the previously when run at shorter periods of time, is no longer seen, and glucose level is flat from the very beginning at near 0:

I know these profiles are not logical and conflicting, which points to me that the simulation is obviously wrong. How could I fix that? Thanks very much!

Juan Carlos