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V11 Bug: OCT1 Influx expression profile populates on apical side of liver rather than basolateral #2302

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prvmalik opened this issue Aug 8, 2022 · 8 comments

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@prvmalik
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prvmalik commented Aug 8, 2022

Other influx transporters may also be affected. Can be fixed manually of course, but the autopopulate from the Genedb may be misleading.

@prvmalik
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prvmalik commented Aug 8, 2022

Also affects OATP1B1. Probably affects all Influx transporters.

@Yuri05
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Yuri05 commented Aug 8, 2022

Probably affects all Influx transporters.

Seems to affect only known (stored in the PK-Sim DB) Influx transporters.
grafik

@Yuri05 Yuri05 added this to the Version 11 Update 1 milestone Aug 8, 2022
@Yuri05
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Yuri05 commented Aug 9, 2022

@msevestre DB entries are correct, so it's during the transport creation where the fraction basolateral is not properly set - interestingly only if the transporter is available in the PK-Sim DB. When creating an influx transporter which is unknown - fractions are set correctly (like in the screen above)
grafik

@prvmalik
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prvmalik commented Aug 9, 2022

Affects both Liver and kidney. I don't recall the proper default for influx at BBB.

@msevestre
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I don't understand from the screenshots above, what the problem is.

@prvmalik
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prvmalik commented Aug 9, 2022

When you do a database query and import the expression profile for an influx transporter e.g. OCT1, OATP1B1, the "Fraction Apical" in the liver and kidney populates as 1.00 when it should be 0.00. BBB may also be affected.

@Yuri05
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Yuri05 commented Aug 9, 2022

The problem is that when creating those transporters, they are defined as basolateral in liver and kidney but created as apical.
So the highlighted fraction_expressed_apical below must be 0, not 1
(Brain and other organs are OK)
grafik

@msevestre msevestre moved this to Todo in V11 - Update 1 Sep 8, 2022
@msevestre
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Well not surprising. We are not using the membrane anymore. The concept of basolateral, apical etc.. was completely removed from PKsim in favor of the fraction expressed. I guess this part was not properly understood during the migration

msevestre added a commit that referenced this issue Sep 9, 2022
msevestre added a commit that referenced this issue Sep 9, 2022
msevestre added a commit that referenced this issue Sep 9, 2022
msevestre added a commit that referenced this issue Sep 12, 2022
Repository owner moved this from Todo to Done in V11 - Update 1 Sep 12, 2022
@Yuri05 Yuri05 moved this from Done to Verified in V11 - Update 1 Dec 27, 2022
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