The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems
Fig 6
An example of a sloppy system.
Observations of an EGFR signaling network can be explained by a model that is identifiable and not sloppy. The 18 parameter model has FIM eigenvalues that span fewer than 4 orders of magnitude and are all larger than one. By including additional mechanisms in the model (more parameters) the models become increasingly sloppy and less identifiable. The FIM eigenvalues ultimately span more than 16 orders of magnitude, leading to the large parameter uncertainties reported in reference [7].