Computational systems biology of the cell cycle.

One of the early success stories of computational systems biology was the work done on cell-cycle regulation. The earliest mathematical descriptions of cell-cycle control evolved into very complex, detailed computational models that describe the regulation of cell division in many different cell types. On the way these models predicted several dynamical properties and unknown components of the system that were later experimentally verified/identified. Still, research on this field is far from over. We need to understand how the core cell-cycle machinery is controlled by internal and external signals, also in yeast cells and in the more complex regulatory networks of higher eukaryotes. Furthermore, there are many computational challenges what we face as new types of data appear thanks to continuing advances in experimental techniques. We have to deal with cell-to-cell variations, revealed by single cell measurements, as well as the tremendous amount of data flowing from high throughput machines. We need new computational concepts and tools to handle these data and develop more detailed, more precise models of cell-cycle regulation in various organisms. Here we review past and present of computational modeling of cell-cycle regulation, and discuss possible future directions of the field.