A cell size- and cell cycle-aware stochastic model for predicting time-dynamic gene network activity in individual...

Despite the development of various modeling approaches to predict gene network activity, a time dynamic stochastic model taking into account real-time changes in cell volume and cell cycle stages is still missing.

Here we present a stochastic single-cell model that can be applied to any eukaryotic gene network with any number of components. The model tracks changes in cell volume, DNA replication, and cell division, and dynamically adjusts rates of stochastic reactions based on this information. By tracking cell division, the model can maintain cell lineage information, allowing the researcher to trace the descendants of any single cell and therefore study cell lineage effects. To test the predictive power of our model, we applied it to the canonical galactose network of the yeast Saccharomyces cerevisiae. Using a minimal set of free parameters and across several galactose induction conditions, the model effectively captured several details of the experimentally-obtained single-cell network activity levels as well as phenotypic switching rates.

Our model can readily be customized to model any gene network in any of the commonly used cells types, offering a novel and user-friendly stochastic modeling capability to the systems biology field.