setting of initial conditions simbiology

Hi, I'm learning the way of creating PKPD model with simbiology

In the example of bacterial PKPD model, there is the discription of "initial conditions" for simulation

But, i was not able to figure out how to set the initial conditions

Initial conditions didn't show up with the MODEL>Tools>Program Initial Conditions Options

It is very helpful to teach me how to manage this !

Thanks,

Answer 1

[Kazutaka Sekiguchi]

Thank you so much, Jérémy

I was following this example https://www.mathworks.com/help/simbio/ug/model-views.html with simbiology app

In this example, variant column and initial conditions seems to be separate

I created the variant for vancomycin, but I was not able to create the column for the initial conditions

what is the difference between "variant" and "initial conditions"?

and, is it difficult to create initial conditions when I use simbiology app?

Best regards,

Kazutaka

[Jeremy Huard]

Dear Kazutaka,

I see what you mean now. The 'Initial conditions' column you see in this example is specific to the selcted program. In this example, the program is called 'Simulation'.

This column is not editable and shows the values at time=0, which are computed from:

• the current model values (the ones that are shown in front of each model component in the Browser)
• any variant that is applied in the selected program
• any dose that is applied in the selected program

So, to change initial conditions for a specific program, you can either change the model values or better, create a dedicated variant for this program and apply it the the program.

To see the initial conditions, first, select Show Programs on the Model tab. Then select a program in the program toolbar.

I hope it helps.

Best regards,

Jérémy

[Kazutaka Sekiguchi]

Thank you for your reply

I would like to ask you about the basics.

When I click "Show Programs" on the Model tab, Select Program was shown up, but I was not able to select anything.

What is the meaning of "Program" in the simbiology? How can I define it?

Best regards,

Kazutaka

[Jeremy Huard]

Dear Kazutaka,

a program defines any analysis you would do in the Model Analyzer App using a model and/or data. This could be a simulation, a parameter scan, a fit, NCA, etc.

You might find the following video useful to create a program: SimBiology Tutorials: Simulating a Model in SimBiology.

There are a few more in our series of tutorial, which can help you get started: SimBiology Tutorials for QSP, PBPK, and PK/PD Modeling and Analysis

Best regards,

Jérémy

[Kazutaka Sekiguchi]

Hi Jeremy

Thank you for your reply

I understood the meaning of program!!

Answer 2

[Jeremy Huard]

Dear Kazutaka,

is this the example you are using?: PK/PD Modeling and Simulation to Guide Dosing Strategy for Antibiotics

If so, in this example initial conditions are the ones defined in the model m1 and they are not modified. If you run the script (especially the command sbioloadproject('AntibacterialPKPD.sbproj', 'm1') ), the model will be loaded. Then, if you type in the Command window of MATLAB:

m1.Species

you will see the list of state variables and their initial conditions. Species Growing in compartment [Bacterial Growth Model] is set to 1e7 molecule/milliliter (=CFU/ml) which corresponds to the severe infection case.

If you want to simulate different conditions, you could use one of the following methods:

1. Modify the value in the model itself: After line 62 of the script where the model is loaded, you could add the following lines:

specObj = sbioselect(m1,'Type','Species','Name','Growing');
specObj.InitialAmount = 1e4;    % Moderate infection

If you are using the SimBiology App, you can open the Model Browser and edit the values there.

The drawback of this method is that the value of Growing is changed in the model itself. So, you will need to remember this to make sure you are simulating the right initial conditions.

2. Use a variant: Variants are constructs that store alternate values of model parameters and initial conditions and are applied at simulation time. Using variant gives you a lot of flexibility and might be easier to keep track of the parameter values and initial conditions used for simulation.

Typically, you would create variants in the SimBiology App with one of the following methods:

a. drag and drop the variant icon into the list of model components in the Model Browser.

b. or open the list of Variants from the 'Open' menu in the 'Model' tab

But you could also define them programmatically:

variant = addvariant(m1, 'Moderate infection');
addcontent(variant, {'species', 'Growing', 'InitialAmount', 1e4});

In this example, you could then use this variant as baseline of the SimFunction:

simfunc = createSimFunction(m1,params,observables,tempdose,variant,'UseParallel',true); % line 239

3. Define this initial value as input of the SimFunction: In the previous methods, the new initial condition will be used for all simulations. But if you wish to be able to change the initial condition for every simulation, it might be better to define the initial amount of the species Growing as input of the SimFunction. SimFunctions are function-like interface to execute SimBiology models with a predefined list of inputs (initial conditions or parameter values) and a predefined list of outputs (e.g. timecourse of some state variables). To implement it you will need to modify line 221 to define the species initial amount as input:

params = {'Central', 'k12', 'k21', 'CL', 'k1', 'k2', 'Kmax', 'KC50','[Bacterial Growth Model].Growing'};

Then, you would need to add the new values of Growing in phi (the matrix containing all values to use for simulation). For instance, if you want to use the same values for all simulations:

iniInfection = 1e4; % new initial condition for species Growing

phi = cell(1,nDoseGrps);
for i = 1:nDoseGrps
    phi{i} = [Central(:,i),k12(:,i),k21(:,i), ...
              CL(:,i), k1(:,i), k2(:,i), ...
              Kmax(:,i), KC50(:,i), iniInfection];
end

But again, this method will be more useful if the the value of Growing differs for the different simulations.

This turned out to be a long answer but I hope it gives you a good overview on how to change initial conditions.

Best regards,

Jérémy