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The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems

Fig 4

FIM for the four EGFR models.

Both the approximate Michaelis-Menten kinetics and mechanistic mass-action kinetics are unidentifiable when fit to the data in reference [7]. Although the optimal experiments in reference [13] lead to an identifiable (but still sloppy) model for the approximate Michaelis-Menten kinetics, the mechanistic mass-action kinetics remain unidentifiable. Furthermore, the FIM of the mass-action model suggests that a minimal model should include at least 60 parameters to explain the expanded observations, i.e., the manifold has approximately 60 widths larger than the experimental noise. The approximate Michaelis-Menten kinetics do not contain all of the relevant physics. The red dashed line corresonds to a relative standard error of 1/e in the inferred parameters.

Fig 4

doi: https://doi.org/10.1371/journal.pcbi.1005227.g004