Alterations in "Distribution" "Permeability" and "intestinal solubility" parameters not indicated

[HenrikCordes]

Dear Developers,

when the intestinal permeability parameter is changed in a simulation:

this is not indicated in the "Simulaitons" sub-window If I change for example of the logP or enzyme expression value, this is indicated:

Is there a reason for this? My understanding is that values in the "Distribution" "Permeability" and "intestinal solubility" tabs are calculated from multiple building blocks and therefore "no alteration" took place in a building block.

Quite often I ran into the issue that I have cloned a simulation and forgot to reset the intestinal permeability in the new simulation because it is not indicated that the simulation deviates form the building blocks.

My feeling would be that if a parameters deviate from the default this should be indicated as deviation somehow. Same goes for all parameters in the "Distribution" "Permeability" and "intestinal solubility" tabs of a simulation. What do you think?

Kind regards, Henrik

[teutonicod]

Dear Henrik,

I absolutely agree with you! Thanks for posting this issue! I also think that this should be marked in the simulation, and the same issue appears also with the B/P ratio; also if it is modified, it is not shown as changed in the simulation.

Thanks, Donato

[Yuri05]

Is there a reason for this? My understanding is that values in the "Distribution" "Permeability" and "intestinal solubility" tabs are calculated from multiple building blocks and therefore "no alteration" took place in a building block.

Your understanding is correct.

Quite often I ran into the issue that I have cloned a simulation and forgot to reset the intestinal permeability in the new simulation because it is not indicated that the simulation deviates form the building blocks.

You can check for all parameters entered or modified by user in a simulation under the User Defined parameters node. Then you can decide which of those parameters you would like to reset in the cloned simulation. (and if you would like to reset ALL parameters which were modified in a simulation - it's easier to create a new simulation from building blocks instead of cloning)

My feeling would be that if a parameters deviate from the default this should be indicated as deviation somehow. Same goes for all parameters in the "Distribution" "Permeability" and "intestinal solubility" tabs of a simulation.

Currently a simulation is only marked as modified only if any of building block parameters within a simulation was changed. Theoretically a simulation could be also marked as modified if one of non-building-block parameters was changed. However the current modified state (i.e. "building block parameter modified within a simulation" state) is used to check if some operations are allowed or not (e.g. cloning of a simulation, exporting a project to snapshot etc.). Extending it to "any parameter modified within a simulation" would increase complexity of the program logic and I am not sure if it is worth it.

[HenrikCordes]

Dear @Yuri05,

thank you for pointing me to the "user defined" Tab in the simulation! That will make the QC much easier for me.

Theoretically a simulation could be also marked as modified if one of non-building-block parameters was changed. However the current modified state (i.e. "building block parameter modified within a simulation" state) is used to check if some operations are allowed or not (e.g. cloning of a simulation, exporting a project to snapshot etc.). Extending it to "any parameter modified within a simulation" would increase complexity of the program logic and I am not sure if it is worth it.

My point of view would be that if cloning of a simulation with modified building block settings is not allowed, why would it for altered simulation parameters? In both cases, the resulting simulation is not in the default setting.

To me it would make sense to allow cloning of a simulation regardless if parameters are modified, but, the resulting model should either be reset into its default state, or left modified. Ideally one could choose this like in the "scaling" option of the individual building block. (Feature request #1292)

What do you think?

Kind regards, Henrik

[teutonicod]

Hi @Yuri05 ,

But in the case of the intestinal permeability, the value is available in the compound building block, so I would expect that if this value is modified, it should be marked as changed with a red flag.

As @HenrikCordes, I would also be happy to have the possibility to clone a simulation also if parameters have been modified :-)

Donato

[msevestre]

But in the case of the intestinal permeability, the value is available in the compound building block, so I would expect that if this value is modified, it should be marked as changed with a red flag.

Not if the value is the calculated value.

[Yuri05]

@HenrikCordes

My point of view would be that if cloning of a simulation with modified building block settings is not allowed, why would it for altered simulation parameters?

It's more for the technical reasons (not so easy to implement 😄 )

To me it would make sense to allow cloning of a simulation regardless if parameters are modified, but, the resulting model should either be reset into its default state, or left modified. Ideally one could choose this like in the "scaling" option of the individual building block.

Please create a feature request for this and we can discuss it there.

@teutonicod

But in the case of the intestinal permeability, the value is available in the compound building block, so I would expect that if this value is modified, it should be marked as changed with a red flag.

It's more complicated here. In fact, those 2 parameters are different. If you look at the formula of Intestinal permeability (transcellular), you will see that it's defined as following: Intestinal permeability (transcellular) = f(P_int_InVitro, m, b) where _P_intInVitro is the Specific intestinal permeability (transcellular) defined in compound building block. This was done to enable user-defined calibration between Caco-2/PAMPA intestinal permeabilities and default "PK-Sim" intestinal permeability (btw. this might also answer your question #352 😉 ) As per default m=1 and b=0 (no calibration). Both parameters m and b are currently hidden in PK-Sim; if you export a simulation to MoBi you can change them (and also a calibration equation if you have another formula for that)