Modular logical modelling of the budding yeast cell cycle

Abstract

Systems biologists are facing the difficult challenge of modelling and analysing regulatory networks encompassing numerous and diverse components and interactions. Furthermore, available data sets are often qualitative, which complicates the definition of truly quantitative models. In order to build comprehensive and predictive models, there is clearly a need for incremental strategies, enabling the progression from relatively small to large scale models. Leaning on former models, we have defined a logical model for three regulatory modules involved in the control of the mitotic cell cycle in budding yeast, namely the core cell cycle module, the morphogenetic checkpoint, and a module controlling the exit from mitosis. Consistency with available data has been assessed through a systematic analysis of model behaviours for various genetic backgrounds and other perturbations. Next, we take advantage of compositional facilities of the logical formalism to combine these three models in order to generate a single comprehensive model involving over thirty regulatory components. The resulting logical model preserves all relevant characteristics of the original modules, while enabling the simulation of more sophisticated experiments.