Some reactions never have any flow after EFM analysis

[ThomasCronimus]

My model is a sbml document and when I doing an EFM some reactions (50, 53, 54, 62, 66, 77, 79 and 80) have never flux. It seems it is note a problem of mass or charge balance. I tried to change the bounds of these reactions (make them reversible or force a minimal flux). I'm desperate.

To Reproduce
Steps to reproduce the behavior:

1. Take this document (I hope it work) and open the zip file to find the sbml model.

Model Thomas Cronimus.zip

2. Open this document in CNApy with the option "New project from SBML".
3. Make a EFM and click on "Reaction participation".
4. The reactions I have listed have a flux of 0.

Expected behavior
I need to have at least Biomass reaction that work. But I don't see any problem in them.

Screenshots

Please complete the following information:

• OS: [windows 11]
• Python version [3.10.16]

Additional context
I ha ve nothing other to say. Thank you for your time.
Best regards,
Thomas Cronimus

[Paulocracy]

Hello and thank you for submitting the issue :D and your SBML loads fine in CNApy :-)

Now regarding your issue: When I run e.g. a Flux Variability Analysis (minimize and maximize all possible fluxes), I can indeed also see that the biomass reaction cannot have any flux (i.e. its minimal and maximal possible flux is just 0 :-/).
Hence, it is seems to be not a CNApy-specific but a model-specific problem as the stoichiometries and/or the set of reactions in the model are configured such that no biomass flux is possible at all D:

I fiddled around a bit with the model, trying to delete biomass components and/or metabolites, but so far nothing conclusive came out of it :-/ But I noticed that phosphate doesn't seem to be able to be imported (at least the pstAS reaction is blocked) and sulfate also seems to have such problems? Also, I noticed that no surplus of ATP or ADP seems to be able to be produced?
It might all be just a small problem but I agreee that it's tricky to identify :3

I just have two general suggestions to try to debug your model further:

1. Try to create a reduced model first, e.g. just with the glycolysis, and see if that works and also e.g. yields the ATP gain you expect
2. Try to put some subpathways in CNApy's native interactive (or Escher) map and see how it behaves

I'm sorry for not being able to help more so far :-/

[ThomasCronimus]

Hello,
First, thank you very much for you answer ! I have made some progress in my work to fix this problem. I have recreat the biomass reaction adding each metabolite one by one. And for all metabolites, except glutamine and gluatamate (GLN and GLT), the reaction and the model work. By this I mean that if you remove GLN and GLT in the Biomass reaction the only reactions that don't work are importation and exchange of ammonium (66 and 77). It makes sense because the "Nitrogen pathway" i.e. reactions 63 to 69 (it is not the good name, I am sorry, I am only student) can be independant, but because GLN and GLT are never consume the model don't need to import nitrogen. Now I tried to understand why Biomass reaction don't work if I put GLN and GLT into.

[Paulocracy]

Hello again :-) I had some trouble in reproducing what you wrote, at least for me, removing removing GLN and GLT in the Biomass reaction doesn't help? Did you maybe change your model?
But the mechanism you found is plausible, maybe other metabolites are affected like this as well :3