Simulation Details
To predict the time evolution of the concentration of metabolites, biochemical system simulators (MATLAB/COPASI) recast the system as a series of coupled ordinary differential equations (ODE) and solve them numerically. The result of these calculations is a simulation, where each model variant predicts of how the metabolite levels change over time.
The simulations described in this work take place over seven simulated hours, where the first hour allows the system to reach a steady state given the initial conditions. At t1h there is the optional event which mimics stimulation and then the simulation runs for 6h. The event at t1h allows the user to release AA and thus activate the eicosanoid cascade. Upon simulating the stimulation at t1h, the time is referred to as t0h post stimulation in all simulations in this study. The time frame post stimulation was arbitrarily chosen as 6h based on the validation studies. The length of time that the simulation predicts can be amended depending on the user. In addition, the COX-2 induction switch can be triggered and the concentration of AA release can be changed at any point during the simulation. The step size for every simulation was 0.5 seconds to ensure good resolution. In the ensemble of models, the number of model variants was assigned before the model simulation script was run. For each model scenario in this work, 1000 model variants were run to create an ensemble of models.
