Steffen Waldherr

Steffen Waldherr, Bernard Haasdonk

Background: Stochastic biochemical reaction networks are commonly modelled by the chemical master equation, and can be simulated as first order linear differential equations through a finite state projection. Due to the very high state space dimension of these equations, numerical simulations are computationally expensive. This is a particular problem for analysis tasks requiring repeated simulations for different parameter values. Such tasks are computationally expensive to the point of infeasibility with the chemical master equation. Results: In this article, we apply parametric model order reduction techniques in order to construct accurate low-dimensional parametric models of the chemical master equation. These surrogate models can be used in various parametric analysis task such as identifiability analysis, parameter estimation, or sensitivity analysis. As biological examples, we consider two models for gene regulation networks, a bistable switch and a network displaying stochastic oscillations. Conclusions: The results show that the parametric model reduction yields efficient models of stochastic biochemical reaction networks, and that these models can be useful for systems biology applications involving parametric analysis problems such as parameter exploration, optimization, estimation or sensitivity analysis.

Armin Küper, Robert Dürr, Steffen Waldherr

Multicellular systems play a key role in bioprocess and biomedical engineering. Cell ensembles encountered in these setups show phenotypic variability like size and biochemical composition. As this variability may result in undesired effects in bioreactors, close monitoring of the cell population heterogeneity is important for maximum production output, and accurate control. However, direct measurements are mostly restricted to a few cellular properties. This motivates the application of model-based online estimation techniques for the reconstruction of non-measurable cellular properties. Population balance modeling allows for a natural description of cell-to-cell variability. In this contribution, we present an estimation approach that, in contrast to existing ones, does not rely on a finite-dimensional approximation through grid based discretization of the underlying population balance model. Instead, our so-called characteristics based density estimator employs sample approximations. With two and three-dimensional benchmark examples we demonstrate that our approach is superior to the grid based designs in terms of accuracy and computational demand.

Armin Küper, Steffen Waldherr

In this manuscript we introduce numerical Gaussian process Kalman filtering (GPKF). Numerical Gaussian processes have recently been developed to simulate spatiotemporal models. The contribution of this paper is to embed numerical Gaussian processes into the recursive Kalman filter equations. This embedding enables us to do Kalman filtering on infinite-dimensional systems using Gaussian processes. This is possible because i) we are obtaining a linear model from numerical Gaussian processes, and ii) the states of this model are by definition Gaussian distributed random variables. Convenient properties of the numerical GPKF are that no spatial discretization of the model is necessary, and manual setting up of the Kalman filter, that is fine-tuning the process and measurement noise levels by hand is not required, as they are learned online from the data stream. We showcase the capability of the numerical GPKF in a simulation study of the advection equation.