Parameter estimation in biochemical reaction networks: An observer-based approach
Description
An important bottleneck in the modelling of biological systems is the scarcity of experimental
data on kinetic parameters. Recent advances in measurement technologies increase the feasibility of
infer ring these parameters from time series data (Anguelova et al., 2007; Voit and Almeida, 2004).
We present a methodology for estimating kinetic parameters from time series data, in a way that
is particularly tailored to biological models consisting of nonlinear ordinary differential equations,
in particular for systems in which the nonlinearities are polynomial, such as in mass action or
generalised mass action kinetics, or rational functions of the states, as in Michaelis-Menten or Hill
kinetics.
The proposed approach consists of three steps. First, the system is transformed into an ex-
tended system in observer normal form. The extended system does only depend on structural
information, not on the value of the parameters (Xia and Zeitz, 1997; Fey et al., 2008). This
allows to design a high-gain observer estimating the states of the extended system (Vargas and
Moreno, 2005). As the extended system is not observable everywhere, but only trajectory ob-
servable, the observer can only be an approximate observer. However, the observer error can be
chosen to be arbitrarily small.
In a final step, the parameters are determined based on the observer states, as the unique
solutions of simple nonlinear functions of these states. Thus, the proposed parameter scheme
estimates is a global estimation algorithm.
The parameter estimation methodology is illustrated on a simple model of the circadian rhythm
in neurospora (Leloup et al., 1999). The model contains three species, six reactions and exhibits
autonomous oscillations corresponding to the day-night cycle The proposed observer-based pa-
rameter estimation method is able to recover all parameters, even if the trajectory comes close to
singularities of the observability.
| Slides | |
| 0:00 | Parameter estimation in biochemical reaction networks: An observer-based approach |
| 0:00 | Outline - 1 |
| 0:33 | Systems biology concept |
| 1:46 | Outline - 2 |
| 2:16 | Motivation |
| 3:17 | Identification of biochemical systems |
| 6:34 | Identifiability |
| 7:34 | Parameter estimation via state observer |
| 10:27 | Event-based observer |
| 10:52 | Overview of proposed parameter estimation |
| 11:11 | Simple model of circadian rhythm |
| 11:37 | Simple model: Extended system |
| 12:02 | Simple model: Output |
| 12:35 | Problem: Singular points |
| 12:47 | Simulation results — States |
| 12:53 | Simulation results — Parameters |
| 13:23 | Summary |
| 13:46 | - Questions |
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