How to deal with parameters for whole-cell modelling

Dynamical systems describing whole cells are on the verge of becoming a reality. But as models of reality, they are only useful if we have realistic parameters for the molecular reaction rates and cell physiological processes. There is currently no suitable framework to reliably estimate hundreds, let alone thousands, of reaction rate parameters. Here, we map out the relative weaknesses and promises of different approaches aimed at redressing this issue. While suitable procedures for estimation or inference of the whole (vast) set of parameters will, in all likelihood, remain elusive, some hope can be drawn from the fact that much of the cellular behaviour may be explained in terms of smaller sets of parameters. Identifying such parameter sets and assessing their behaviour is now becoming possible even for very large systems of equations, and we expect such methods to become central tools in the development and analysis of whole-cell models.