Estimation methods for heterogeneous cell population models in systems biology.

Heterogeneity among individual cells is a characteristic and relevant feature of living systems. A range of experimental techniques to investigate this heterogeneity is available, and multiple modelling frameworks have been developed to describe and simulate the dynamics of heterogeneous populations. Measurement data are used to adjust computational models, which results in parameter and state estimation problems. Methods to solve these estimation problems need to take the specific properties of data and models into account. The aim of this review is to give an overview on the state of the art in estimation methods for heterogeneous cell population data and models. The focus is on models based on the population balance equation, but stochastic and individual-based models are also discussed. It starts with a brief discussion of common experimental approaches and types of measurement data that can be obtained in this context. The second part describes computational modelling frameworks for heterogeneous populations and the types of estimation problems occurring for these models. The third part starts with a discussion of observability and identifiability properties, after which the computational methods to solve the various estimation problems are described.