Parameter estimation in kinetic reaction models using nonlinear observers facilitated by model extensions

An essential part of mathematical modelling is the accurate and reliable estimation of model parameters. In biology, the required parameters are particularly difficult to measure due to either shortcomings of the measurement technology or a lack of direct measurements. In both cases, parameters must be estimated from indirect measurements, usually in the form of time-series data. Here, we present a novel approach for parameter estimation that is particularly tailored to biological models consisting of nonlinear ordinary differential equations. By assuming specific types of nonlinearities common in biology, resulting from generalised mass action, Hill kinetics and products thereof, we can take a three step approach: (1) transform the identification into an observer problem using a suitable model extension that decouples the estimation of non-measured states from the parameters; (2) reconstruct all extended states using suitable nonlinear observers; (3) estimate the parameters using the reconstructed states. The actual estimation of the parameters is based on the intrinsic dependencies of the extended states arising from the definitions of the extended variables. An important advantage of the proposed method is that it allows to identify suitable measurements and/or model structures for which the parameters can be estimated. Furthermore, the proposed identification approach is generally applicable to models of metabolic networks, signal transduction and gene regulation

Inference of nonlinear state-space models for sandwich-type lateral flow immunoassay using extended Kalman filtering

Copyright [2011] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In this paper, a mathematical model for sandwichtype lateral flow immunoassay is developed via short available time series. A nonlinear dynamic stochastic model is considered that consists of the biochemical reaction system equations and the observation equation. After specifying the model structure, we apply the extend Kalman filter (EKF) algorithm for identifying both the states and parameters of the nonlinear state-space model. It is shown that the EKF algorithm can accurately identify the parameters and also predict the system states in the nonlinear dynamic stochastic model through an iterative procedure by using a small number of observations. The identified mathematical model provides a powerful tool for testing the system hypotheses and also inspecting the effects from various design parameters in a both rapid and inexpensive way. Furthermore, by means of the established model, the dynamic changes of the concentration of antigens and antibodies can be predicted, thereby making it possible for us to analyze, optimize and design the properties of lateral flow immunoassay devices.This work was supported in part by the International Science and Technology Cooperation Project of China under Grant 2009DFA32050, Natural Science Foundation of Fujian Province of China under Grants 2009J01280 and 2009J01281

Direct estimation of kinetic parametric images for dynamic PET.

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed

Comparisons of nonlinear estimators for wastewater treatment plants

This paper deals with five existing nonlinear estimators (filters), which include Extended Kalman Filter (EKF), Extended H-infinity Filter (EHF), State Dependent Filter (SDF), State Dependent H-Infinity Filter (SDHF) and Unscented Kalman Filter (UKF) that are formulated and implemented to estimate unmeasured states of a typical biological wastewater system. The performance of these five estimators of different complexities, behaviour and advantages are demonstrated and compared via nonlinear simulations. This study shows promising application of UKF for monitoring and control of the process variables, which are not directly measurable

A Probabilistic Approach to Robust Optimal Experiment Design with Chance Constraints

Accurate estimation of parameters is paramount in developing high-fidelity models for complex dynamical systems. Model-based optimal experiment design (OED) approaches enable systematic design of dynamic experiments to generate input-output data sets with high information content for parameter estimation. Standard OED approaches however face two challenges: (i) experiment design under incomplete system information due to unknown true parameters, which usually requires many iterations of OED; (ii) incapability of systematically accounting for the inherent uncertainties of complex systems, which can lead to diminished effectiveness of the designed optimal excitation signal as well as violation of system constraints. This paper presents a robust OED approach for nonlinear systems with arbitrarily-shaped time-invariant probabilistic uncertainties. Polynomial chaos is used for efficient uncertainty propagation. The distinct feature of the robust OED approach is the inclusion of chance constraints to ensure constraint satisfaction in a stochastic setting. The presented approach is demonstrated by optimal experimental design for the JAK-STAT5 signaling pathway that regulates various cellular processes in a biological cell.Comment: Submitted to ADCHEM 201

Determine measurement set for parameter estimation in biological systems modeling

Parameter estimation is challenging for biological systems modelling since the model is normally of high dimension, the measurement data are sparse and noisy, and the cost of experiments is high. Accurate recovery of parameters depend on the quantity and quality of measurement data. It is therefore important to know what measurements to be taken, when and how through optimal experimental design (OED). In this paper we present a method to determine the most informative measurement set for parameter estimation of dynamic systems, in particular biochemical reaction systems, such that the unknown parameters can be inferred with the best possible statistical quality using the data collected from the designed experiments. System analysis using matrix theory is introduced to examine the number of necessary measurement variables. The priority of each measurement variable is determined by optimal experimental design based on Fisher information matrix (FIM). The applicability and advantages of the proposed method are illustrated through an example of a signal pathway model

Adaptive optimal operation of a parallel robotic liquid handling station

Results are presented from the optimal operation of a fully automated robotic liquid handling station where parallel experiments are performed for calibrating a kinetic fermentation model. To increase the robustness against uncertainties and/or wrong assumptions about the parameter values, an iterative calibration and experiment design approach is adopted. Its implementation yields a stepwise reduction of parameter uncertainties together with an adaptive redesign of reactor feeding strategies whenever new measurement information is available. The case study considers the adaptive optimal design of 4 parallel fed-batch strategies implemented in 8 mini-bioreactors. Details are given on the size and complexity of the problem and the challenges related to calibration of over-parameterized models and scarce and non-informative measurement data. It is shown how methods for parameter identifiability analysis and numerical regularization can be used for monitoring the progress of the experimental campaigns in terms of generated information regarding parameters and selection of the best fitting parameter subset.BMBF, 02PJ1150, Verbundprojekt: Plattformtechnologien für automatisierte Bioprozessentwicklung (AutoBio); Teilprojekt: Automatisierte Bioprozessentwicklung am Beispiel von neuen Nukleosidphosphorylase

A hybrid EKF and switching PSO algorithm for joint state and parameter estimation of lateral flow immunoassay models

This is the post-print version of the Article. The official published can be accessed from the link below - Copyright @ 2012 IEEEIn this paper, a hybrid extended Kalman filter (EKF) and switching particle swarm optimization (SPSO) algorithm is proposed for jointly estimating both the parameters and states of the lateral flow immunoassay model through available short time-series measurement. Our proposed method generalizes the well-known EKF algorithm by imposing physical constraints on the system states. Note that the state constraints are encountered very often in practice that give rise to considerable difficulties in system analysis and design. The main purpose of this paper is to handle the dynamic modeling problem with state constraints by combining the extended Kalman filtering and constrained optimization algorithms via the maximization probability method. More specifically, a recently developed SPSO algorithm is used to cope with the constrained optimization problem by converting it into an unconstrained optimization one through adding a penalty term to the objective function. The proposed algorithm is then employed to simultaneously identify the parameters and states of a lateral flow immunoassay model. It is shown that the proposed algorithm gives much improved performance over the traditional EKF method.This work was supported in part by the International Science and Technology Cooperation Project of China under Grant 2009DFA32050, Natural Science Foundation of China under Grants 61104041, International Science and Technology Cooperation Project of Fujian Province of China under Grant 2009I0016