Figure 2. The novel viewpoint provided by sensitivity analysis.

(A) A simulation may be conceived as simply a transformation from a set of equations into meaningful output, such as cellular transmembrane potential (V) and cytosolic Ca²⁺ concentration. The questions of greater interest, however, often concern the predicted changes in physiological outputs due to alterations caused by drugs or disease states. These questions generally cannot be addressed by the model equations themselves, but they can be addressed by systematically perturbing the model, i.e. performing a sensitivity analysis. (B) Once this has been performed, the investigator has a higher-level viewpoint of the model. It can now be seen as transforming changes in model parameters into altered physiological phenotypes.