Resetting initial concentrations in the simulation and is not propagated to BB after commit

[Yuri05]

In the example from #2253 I click on the Reset button in the initial concentration in the simulation

Then I commit the Individual from the simulation back to the BB.

• In the Individual-BB the value is correctly resetted to 0 (btw, suddenly I see an entry for Endosome initial concentration which was not shown before. Why?)
  
• But in the Protein-Expression-BB the value is still 1. Closing/Reopening the Protein-Expression-BB does not help, so it's not a refresh progress. And also here I suddenly get the entry for Endosome...
  

[msevestre]

@Yuri05
I don't understand what you mean with Endosome

it's always their as soon as you show initial concentration in expression profile

[msevestre]

@Yuri05
I do not have a reset button in the simulation

it is now a constant with value 1. Probably because of the fix in #2253

[msevestre]

and in fact I would expect this behavior

[msevestre]

So as far as I am concerned, this is fixed. Closing. Please reopen if this is not the case

[Yuri05]

OK, Endosome is always shown now. Pretty sure it was not the case before - anyway, now it's consistent, so all good.

Regarding the rest of the issue: now the behaviour is different. There is no reset button in the simulation indeed.
But what happens after committing changed initial conc value from simulation to individual - not sure if it is correct.

E.g. in the project attached P1_2.zip:

• I have set Bone|Intracellular|CYP|Initial Concentration = 2 in the Protein Expression BB, then created an Individual and a simulation with it
• In the simulation I have ovewritten this initial concetration with 20 and commited the individual into the BB
• After that I have the following situation
  • In the Expression Profile BB, the value is 2 and the Reset button is active. If I click on it: the value is resetted back to NaN and the button disappears (correct bahaviour I guess)
    
  • In the individual BB, the value is 20 (correct) and the Reset button is active. If I click on it: nothing happens (value remains =20, Reset button remains active)
    
  • OK, just noticed: the situation with non-working Reset button in individual is already after adding the enzyme to it. So if create another individual and add my enzyme: the value of the initial concentration is the one from the expression profile BB (correct) and the Reset button is active without any effect. I have created another issues for this: When overwriting initial protein concentration in Expression Profile BB: Reset button is active in Individual with no effect #2270

[msevestre]

I can't reproduce your other issue.
On a NEW Simulation (so that the formula is not taken but a constant as implemented)

• If I am setting a value in the simulation (say 10)
  
• Commit to bb
  
  In individual I have
  

and in expression profile I have

This will only work with new simulations but I think the behavior is correct

[msevestre]

Please reopen and explain if this is not desired

[PavelBal]

@Yuri05 so you do not miss it.

[Yuri05]

At the moment (PK-Sim 11.1.110) the behaviour is different from described here(#2255 (comment))

E.g. in this project P10_IC.zip I set all relExp=1 in the protein-expressions-BB (thus the initial concentrations in all intracellular compartments have some non-zero values), then added the enzyme to an individual nad created a simulation:

After this, I have overwritten some intracellular initial concentrations in the simulation with the value 10 and commited the individual from the simulation back to the building block (the result is in this project: P10_IC_changed_in_Sim.zip

This changed the values to 10 in the individual:

But not in the expression profile used:

P.S. If after that I change any value in my expression profile: all intracellular initial concentrations in the individual jump from 10 to another values.

@msevestre @PavelBal

[PavelBal]

This changed the values to 10 in the individual:
But not in the expression profile used:

I would say this is the correct behavior.

P.S. If after that I change any value in my expression profile: all intracellular initial concentrations in the individual jump from 10 to another values.

This I consider as a bug. The values in the individuals should only jump when explicitely updating from Expressions BB.

[msevestre]

@Yuri05 I have tried yesterday and today to reproduce the issue but I can't
Can you show me how to reproduce? I don't even see a refresh problem

So I am not sure with which version you tried. But I can't reproduce and I have spent just too much time trying lol.

[Yuri05]

Tricky indeed :) I could finally reproduce with the latest nightly 11.1.126. Below the steps to reproduce.

The interesting part: if I save the project after step 5 ("Create simulation"), reopen it and continue with the step 6 - everything works fine. Thus I could not reproduce the problem with the project which I attached above as well :)
But if you create everything from scratch as described below - here we go :)

1. Add enzyme CYP and set all relative expressions = 1

Screen

2. Add Individual and add CYP to individual

3. Add arbitrary compound

4. Add arbitrary application

5. Create simulation

6. In the simulation: set intracellular initial concentration of all tissue organs = 10

Screen

7. Commit Individual from the simulation to BB

8. Go to the Expression profile and check intracellular initial concentrations: they are not set

Screen

If I save the project NOW and reopen it: initial concentrations in the expression profile are still not set, so it's not just a refresh issue.

[msevestre]

I spent so much time on this....
Ok doest not feel like such a bad bug after all

[Yuri05]

doest not feel like such a bad bug after all

Not sure about this. Seems we create some corrupted state here - no idea what other side effects this could have.
For example, if I save the project at the end of the whole workflow above, reopen it and change anything in my expression profile: all initial concentrations in the individual become resetted etc.

Can you reproduce with the steps above?

[msevestre]

I'll try in the afternoon today. It's good to have at least a way to reproduce
And I didn't read that the state was corrupted when the project was saved to I might be able to see what's missing

[msevestre]

@Yuri05 This with saving project was key to understand what's going on. this had to be a registration issues
After good 5 hours of debugging in two days, I think I understand. Even debugging visually because it was so hard to understand lol