Numerical Parameter Space Compression and Its Application to Biophysical Models.

Physical models of biological systems can become difficult to interpret when they have a large number of parameters. But the models themselves actually depend on (i.e., are sensitive to) only a subset of those parameters. This phenomenon is due to parameter space compression (PSC), in which a subset of parameters emerges as "stiff" as a function of time or space. PSC has only been used to explain analytically solvable physics models. We have generalized this result by developing a numerical approach to PSC that can be applied to any computational model. We validated our method against analytically solvable models of a random walk with drift and protein production and degradation. We then applied our method to a simple computational model of microtubule dynamic instability. We propose that numerical PSC has the potential to identify the low-dimensional structure of many computational models in biophysics. The low-dimensional structure of a model is easier to interpret and identifies the mechanisms and experiments that best characterize the system.