Struggling with COPASI plots – student seeking guidance

[Sara Biamonte]

Dear all, 

I am a University student working on a Systems Biology project and I'm trying to reproduce all the plots from "Full-scale model of glycolysis in Saccharomyces cerevisiae", by Hynne et Al. (2001)- Hynne2001_Glycolysis | BioModels. Unfortunaltely, I have been struggling a lot and I can't manage to generate them correctly (except for fig. 6), despite all the efforts and time I've spent on trying. I already tried to ask my professors for help, but unfortunately I did not receive a reply.

For Figure 4, panel (b), I tried to perform a time course with the bifurcation value of the species "mixed flow glucose" (18.5 mM), but the output is definitely not the same as in the paper. I have attached a screenshot showing the output I get ("Concentrations, Volumes and Global Quantity Values"). I also tried to start from steady state and then to trigger the system, but it still didn't work. It seemed to me that COPASI did not consider the same bifurcation value as the paper, so I tried to determine it manually, but I still obtained oscillations. 

Then I tried to reproduce the bifurcation plot in Figure 5 using the Parameter Scan task, but as you can see in my screenshot "Bifurcation plot", I obtained only one "branch". I also made an attempt using the Cross Section task, but this did not solve my problems either. 

Finally, regarding the Quenching plots, I tried to calculate the time of the oscillations in order to determine the right one to apply the triggers. My results were completely different from the plots in the paper, and to make them look similar I had to radically change the trigger concentration (and the time as well). 

I have made many attempts and tried everything I could, so I would like to understand whether the issue is due to something I am doing wrong, or if these plots are actually not possible to replicate properly in COPASI.

Thank you very much in advance for your help. 

Kind regards, 

Sara Biamonte

[Matthias König]

Hi Sara,

reproducing existing models and simulations can be very challenging.

In your case, you’re working with a curated BioModels entry. This means the curation team has already invested effort into reproducing the key plots from the original paper. You might find the additional resources on BioModels helpful:
https://www.ebi.ac.uk/biomodels/BIOMD0000000061#Files

Figure 6, for example, was successfully reproduced by the team using COPASI. You could request access to their COPASI file to get started. I would recommend beginning with Figure 6, since others have already managed to reproduce it.

Best,
Matthias

[Sara Biamonte]

Hi all, 

I just wanted to follow up on my previous message. 

To clarify, I downloaded the SBML model directly from BioModels and imported it into COPASI. I was able to reproduce only Figure 6 correctly — none of the other figures (Figure 4, Figure 5, or the quenching plots) match the results reported in the paper.  

I have tried three different methods for generating the bifurcation plots (and the other figures, too), but the outcome was never correct. Could you please confirm whether this model can actually reproduce these figures in COPASI? 

Any detailed guidance or clarification would be greatly appreciated.  

Best regards, 

Sara

[Matthias König]

Hi Sara,

I tried to reproduce Figures 4 and 5 and obtained the same results you shared. The bifurcation behavior reported in those figures cannot be reproduced with the current model, and I observe the same NADH curves as you showed.

I double-checked the parameters, and everything appears consistent with the publication. Specifically, I downloaded the model and varied the external glucose concentrations to 17, 18.5, and 20 mM. The results in libRoadRunner match those from COPASI, so this is not a software issue. It seems that the model available is simply not the one that generated Figures 4 and 5 — most likely, additional parameter changes were made but not reported.

My understanding is that, within the Biomodels reproducibility effort, only Figure 6 could be successfully reproduced. Figures 4 and 5 have never been replicated with the current model. Since Biomodels only requires that a single figure from the publication be reproducible for curation, inclusion in the curated branch doesn’t imply that all figures or results can be reproduced.

I would recommend getting in touch with the original authors and requesting the code or scripts used for the analysis of Figures 4 and 5. This might clarify which additional parameters or settings were applied.

Best,
Matthias

[Sara Biamonte]

Hi Matthias, 

Thank you very much for taking the time to reproduce the simulations and for your explanation. Your clarification was really helpful — I truly appreciate your effort.  I’ll try to contact the original authors as you suggested. 

Best regards, 

Sara

--
You received this message because you are subscribed to the Google Groups "COPASI User Forum" group.
To unsubscribe from this group and stop receiving emails from it, send an email to copasi-user-fo...@googlegroups.com.
To view this discussion visit https://groups.google.com/d/msgid/copasi-user-forum/1958d624-85d2-41dd-bd44-6d70c715917cn%40googlegroups.com.