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Journal Articles Mathematical Biosciences Year : 2022

Revisiting moment-closure methods with heterogeneous multiscale population models


Stochastic chemical kinetics at the single-cell level give rise to heterogeneous populations of cells even when all individuals are genetically identical. This heterogeneity can lead to nonuniform behaviour within populations, including different growth characteristics, cell-fate dynamics, and response to stimuli. Ultimately, these diverse behaviours lead to intricate population dynamics that are inherently multiscale: the population composition evolves based on population-level processes that interact with stochastically distributed single-cell states. Therefore, descriptions that account for this heterogeneity are essential to accurately model and control chemical processes. However, for real-world systems such models are computationally expensive to simulate, which can make optimisation problems, such as optimal control or parameter inference, prohibitively challenging. Here, we consider a class of multiscale population models that incorporate population-level mechanisms while remaining faithful to the underlying stochasticity at the single-cell level and the interplay between these two scales. To address the complexity, we study an order-reduction approximations based on the distribution moments. Since previous moment-closure work has focused on the single-cell kinetics, extending these techniques to populations models prompts us to revisit old observations as well as tackle new challenges. In this extended multiscale context, we encounter the previously established observation that the simplest closure techniques can lead to non-physical system trajectories. Despite their poor performance in some systems, we provide an example where these simple closures outperform more sophisticated closure methods in accurately, efficiently, and robustly solving the problem of optimal control of bioproduction in a microbial consortium model.
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Dates and versions

hal-03479587 , version 1 (14-12-2021)
hal-03479587 , version 2 (27-06-2022)




Davin Lunz, Joseph Frédéric Bonnans, Jakob Ruess. Revisiting moment-closure methods with heterogeneous multiscale population models. Mathematical Biosciences, 2022, 350, pp.108866. ⟨10.1016/j.mbs.2022.108866⟩. ⟨hal-03479587v2⟩
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