Spatial Structure: Default value for IsPresent and Negative values allowed

[msevestre]

Each SS defines default values of "isPresent" and "Negative values allowed" for certain types of molecules (floating compounds, enzymes, transporters) (selctable via a check-box).

@PavelBal Based on this description, it seems to be a DEFAULT VALUE FOR THE SPATIAL STRUCTURE and not per container. Is this correct? I had the feeling you were mentioning this was per container last time

[PavelBal]

Oh this must be a confusion, this is actually PER CONTAINER.

[msevestre]

Ok so what do we need to save now for each container? do we still need one entry per type (Enzyme, Transproter etc.) Or do we need only two (Floating and Non Floating?). How is this then going to be used? Can you explain again?

[msevestre]

Feedback please

[StephanSchaller]

Is there any similar logic in PK-Sim of how it populates the containers with molecules in the default PBPK model structure? This should be similar. I guess we still need al 3 types as enzymes and transporters might need to be handled differently in terms of localization.

[PavelBal]

The purpose of this feature is to make the extension of the model with new molecules or compartments easier by defining the default values for isPresent, that would apply in most of the cases. In current implementation, all (new) molecules are present in all (new) comparments except for some exceptions (that are not clearly visible to the user), and the user has to adjust this property manually.

With the new implementation of the expression in OSPS V10, life became much easier as all proteins are present in all containers. In the small molecules model, all molecules are present everywhere except for:

• Gallbladder, where all FLOATING molecules are present, but not the proteins.
• Urine, where all FLOATING molecules are present, but not the proteins.
• Feces, where all FLOATING molecules are present, but not the proteins.
• Saliva, where all FLOATING molecules are present, but not the proteins.

For the small molecules model, a simple distinction between "Floating" and "non-floating" would be sufficient.

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In the large molecules model, things are more complicated.

• MOLECULE-FcRn_Complex (floating) are present everywhere BUT:

  • Gallbladder
  • EndosomalClearance
  • Urine
  • Lumen
  • Saliva
  • Intracellular
  • BloodCells
  • Plasma of blood organs (VenousBlood, ArterialBlood, PortalVein)

• FcRn is present in:

  • EndogenousIgG|Plasma
  • EndogenousIgG|Interstitial
  • EndogenousIgG|Endosome

• FcRn kinetics endosome is present in:

  • EndogenousIgG|Endosome

• FcRn kinetics interstitial is present in:

  • EndogenousIgG|Interstitial

• FcRn kinetics plasma is present in:

  • EndogenousIgG|Plasma

• LigandEndo is present in:

  • EndogenousIgG|Plasma
  • EndogenousIgG|Interstitial
  • EndogenousIgG|Endosome
  • EndogenousIgG|IgG_Source
  • EndogenousIgG|EndosomalClearance

• LigandEndo_Complex is present in:

  • EndogenousIgG|Plasma
  • EndogenousIgG|Interstitial
  • EndogenousIgG|Endosome

• In container EndosomalClearance, all floating molecules but MOLECULE-FcRn_Complex

• Each organ gets the compartment Endosome, where all molecules are present, except for the specific molecules for the two-pores model listed below (even proteins are present!)

SUMMARY: this is pretty ugly for the two-pores model and the extension is a pain. Maybe we could re-implement the model with parameters instead of molecules and utilize the sum formulas? @StephanSchaller FYI

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For the feature addressed in this issue - I think implementing the default isPresent for floating and non-floating (or better - stationary and non-stationary) still makes sense. For the molecules and containers involved in the two-pores model, I do not have a solution right now.

[msevestre]

Let's discuss about this today. It doesn't sound to me like we are 💯 convinced that this is high prio. I may read this incorrectly but better be sure before I start working on this feature

[PavelBal]

Meeting 22.02.2023:

• simplify 2 pores model
• Find how special cases (gallbladder, urine, etc) are implemented
• Decide whether this feature will be implemented