Protein expression: "Blood cells" expression is not properly set

[PavelBal]

Add expression of the enzyme "AADAC" from the database.

V9:

V10:

Expression in blood cells is not set.

[msevestre]

Interesting. We did not foresee for this values to be updated from the DB (e.g "Localization")
What should be the logic here? If a value is coming != 0, we need to activate some localization?
Do we have something else than Blood cells?

[PavelBal]

What should be the logic here? If a value is coming != 0, we need to activate some localization?

Yes

Do we have something else than Blood cells?

Could be vascular endothelium.

[msevestre]

We are going to need to specify this. What localization should be turned on automatically based on what parameter values

[PavelBal]

If the value for blood cells != 0:

• If default localization is "Intracellular" -> enable "Blood cells intracellular"
  
• If default localization is "Interstitial" -> enable "Blood cells membrane"
  

If the value for "Vascular endothelium" != 0:

• If default localization in PK-Sim9 is "Endosomal" -> enable "Vascular endothelium endosomes"
• If default localization in PK-Sim9 is "Interstitial" -> enable "Vascular endothelium membrane plasma-side"
• If default localization in PK-Sim9 is "Extracellular membrane + basolateral" -> enable "Vascular endothelium membrane tissue-side"
• If default localization in PK-Sim9 is "Extracellular membrane + apical" -> enable "Vascular endothelium membrane plasma-side"

I guess this covers all cases... Or what localization information do we actually have in the DB?

[msevestre]

There is none localization info in the db. Only expression values.
So the question should be more: what localization should we turn in automatically based on expression values received from db. This happens only upon enzyme creation/update I guess

[Yuri05]

If default localization is "Interstitial" -> enable "Blood cells membrane"

That's not correct.

• "Interstitial" ➡️ "Blood cells intracellular"
• "Extracellular Membrane" ➡️ "Blood cells membrane"
• "Intracellular" ➡️ "Blood cells intracellular"

[Yuri05]

If default localization in PK-Sim9 is "Interstitial" -> enable "Vascular endothelium membrane plasma-side"

Also not correct. must be "Vascular endothelium membrane tissue-side"

[msevestre]

But we have no concept of localization in the protein expression db. We only have expression values....booo

[Yuri05]

Ah, ok, finaly I got what this issue is about (thought it was about project conversion V9=>V10 due to the discussion above).

Yep, we don't have localization in the protein expression DB. So from my point of view:

• if relExp in Blood Cells returned by the DB query is not zero:
  • "Blood cells intracellular" checkbox must be activated
  • Fraction expressed in blood cells must be set to 1 (s. also Default values for Fraction Expressed in Blood Cells and in Endosome not as expected #2053)
• if relExp in Vascular Ensothelium returned by by the DB query is not zero:
  • "Vascular endothelium endosomes" checkbox must be activated
  • Fraction expressed in endosomes must be set to 1 (s. also Default values for Fraction Expressed in Blood Cells and in Endosome not as expected #2053)

In fact what happens at the moment (@prvmalik ): the value of relExp in blood cells is not zero, it's set to the proper value coming from the GeneExpression-DB. However due to the current default value of Fraction expressed in blood cells (0), the protein amount is placed into plasma, which in the most cases is not what is expected, I guess.