When PBPK simulators do not reflect modern physiology

PBPK simulators use a compartmental approach, where fluids are transferred between compartments and transformed inside them.

It is a very mechanistic approach, a successful one, but it ignores many important aspects of Mammalian biology such as the influence of the genome on health or the signaling between cells or throughout the organism, for example with the immune system.

Even the illness or simply the unhealthy human, is not implemented in models, rather they are “cases” that are hard-wired in the software.

It is well known there is a need to separate the model from the simulator, in order to make it possible to change some parameters or even the whole model at will. Every CellML or SBML simulator offers that kind of functionality.

It goes the same way for genetic information, not only it should be taken in account, but it should be separated and accessible in its own set of portable data. I do not know how SBML format would make it possible.

Cell or organism signaling should also be assigned to a distinct set of portable data. We have already something similar for fluids in our current simulator’s PoC, it is separated in a distinct XML file, something unfortunately not standardized.

Therefore we have to think how fluids, genetic information (and variants) as well as signaling or health will be taken in account in future versions of the PoC of our simulator.

In addition we have to offer a multi-faceted GUI, for example a human diabetic model and a dysfunction of insulin production are nearly about the same thing, but they are different ways to discuss about it and they are not the exactly the same topic.