Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF), rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison

Inference in Nonlinear Systems with Unscented Kalman Filters

An increasing number of scientific disciplines, most notably the life sciences and health care, have become more quantitative, describing complex systems with coupled nonlinear di↵erential equations. While powerful algorithms for numerical simulations from these systems have been developed, statistical inference of the system parameters is still a challenging problem. A promising approach is based on the unscented Kalman filter (UKF), which has seen a variety of recent applications, from soft tissue mechanics to chemical kinetics. The present study investigates the dependence of the accuracy of parameter estimation on the initialisation. Based on three toy systems that capture typical features of real-world complex systems: limit cycles, chaotic attractors and intrinsic stochasticity, we carry out repeated simulations on a large range of independent data instantiations. Our study allows a quantification of the accuracy of inference, measured in terms of two alternative distance measures in function and parameter space, in dependence on the initial deviation from the ground truth

An online grey-box model based on unscented kalman filter to predict temperature profiles in smart buildings

Nearly 40% of primary energy consumption is related to the usage of energy in Buildings. Energy-related data such as indoor air temperature and power consumption of heating/cooling systems can be now collected due to the widespread diffusion of Internet-of-Things devices. Such energy data can be used (i) to train data-driven models than learn the thermal properties of buildings and (ii) to predict indoor temperature evolution. In this paper, we present a Grey-box model to estimate thermal dynamics in buildings based on Unscented Kalman Filter and thermal network representation. The proposed methodology has been applied in two different buildings with two different thermal network discretizations to test its accuracy in indoor air temperature prediction. Due to a lack of a real-world data sampled by Internet of Things (IoT) devices, a realistic data-set has been generated using the software Energy+, by referring to real industrial building models. Results on synthetic and realistic data show the accuracy of the proposed methodology in predicting indoor temperature trends up to the next 24 h with a maximum error lower than 2 °C, considering one year of data with different weather conditions

Insulin Estimation and Prediction A REVIEW OF THE ESTIMATION AND PREDICTION OF SUBCUTANEOUS INSULIN PHARMACOKINETICS IN CLOSED-LOOP GLUCOSE CONTROL

This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) through grant DPI2013-46982-C2-1-R and the EU through FEDER funds.Bondía Company, J.; Romero Vivó, S.; Ricarte Benedito, B.; Diez, J. (2018). Insulin Estimation and Prediction A REVIEW OF THE ESTIMATION AND PREDICTION OF SUBCUTANEOUS INSULIN PHARMACOKINETICS IN CLOSED-LOOP GLUCOSE CONTROL. IEEE Control Systems. 38(1):47-66. https://doi.org/10.1109/MCS.2017.2766312S476638

Data assimilation for conductance-based neuronal models

This dissertation illustrates the use of data assimilation algorithms to estimate unobserved variables and unknown parameters of conductance-based neuronal models. Modern data assimilation (DA) techniques are widely used in climate science and weather prediction, but have only recently begun to be applied in neuroscience. The two main classes of DA techniques are sequential methods and variational methods. Throughout this work, twin experiments, where the data is synthetically generated from output of the model, are used to validate use of these techniques for conductance-based models observing only the voltage trace. In Chapter 1, these techniques are described in detail and the estimation problem for conductance-based neuron models is derived. In Chapter 2, these techniques are applied to a minimal conductance-based model, the Morris-Lecar model. This model exhibits qualitatively different types of neuronal excitability due to changes in the underlying bifurcation structure and it is shown that the DA methods can identify parameter sets that produce the correct bifurcation structure even with initial parameter guesses that correspond to a different excitability regime. This demonstrates the ability of DA techniques to perform nonlinear state and parameter estimation, and introduces the geometric structure of inferred models as a novel qualitative measure of estimation success. Chapter 3 extends the ideas of variational data assimilation to include a control term to relax the problem further in a process that is referred to as nudging from the geoscience community. The nudged 4D-Var is applied to twin experiments from a more complex, Hodgkin-Huxley-type two-compartment model for various time-sampling strategies. This controlled 4D-Var with nonuniform time-samplings is then applied to voltage traces from current-clamp recordings of suprachiasmatic nucleus neurons in diurnal rodents to improve upon our understanding of the driving forces in circadian (~24) rhythms of electrical activity. In Chapter 4 the complementary strengths of 4D-Var and UKF are leveraged to create a two-stage algorithm that uses 4D-Var to estimate fast timescale parameters and UKF for slow timescale parameters. This coupled approach is applied to data from a conductance-based model of neuronal bursting with distinctive slow and fast time-scales present in the dynamics. In Chapter 5, the ideas of identifiability and sensitivity are introduced. The Morris-Lecar model and a subset of its parameters are shown to be identifiable through the use of numerical techniques. Chapter 6 frames the selection of stimulus waveforms to inject into neurons during patch-clamp recordings as an optimal experimental design problem. Results on the optimal stimulus waveforms for improving the identifiability of parameters for a Hodgkin-Huxley-type model are presented. Chapter 7 shows the preliminary application of data assimilation for voltage-clamp, rather than current-clamp, data and expands on voltage-clamp principles to formulate a reduced assimilation problem driven by the observed voltage. Concluding thoughts are given in Chapter 8

Comprehensive review of models and methods for inferences in bio-chemical reaction networks

The key processes in biological and chemical systems are described by networks of chemical reactions. From molecular biology to biotechnology applications, computational models of reaction networks are used extensively to elucidate their non-linear dynamics. The model dynamics are crucially dependent on the parameter values which are often estimated from observations. Over the past decade, the interest in parameter and state estimation in models of (bio-) chemical reaction networks (BRNs) grew considerably. The related inference problems are also encountered in many other tasks including model calibration, discrimination, identifiability, and checking, and optimum experiment design, sensitivity analysis, and bifurcation analysis. The aim of this review paper is to examine the developments in literature to understand what BRN models are commonly used, and for what inference tasks and inference methods. The initial collection of about 700 documents concerning estimation problems in BRNs excluding books and textbooks in computational biology and chemistry were screened to select over 270 research papers and 20 graduate research theses. The paper selection was facilitated by text mining scripts to automate the search for relevant keywords and terms. The outcomes are presented in tables revealing the levels of interest in different inference tasks and methods for given models in the literature as well as the research trends are uncovered. Our findings indicate that many combinations of models, tasks and methods are still relatively unexplored, and there are many new research opportunities to explore combinations that have not been considered—perhaps for good reasons. The most common models of BRNs in literature involve differential equations, Markov processes, mass action kinetics, and state space representations whereas the most common tasks are the parameter inference and model identification. The most common methods in literature are Bayesian analysis, Monte Carlo sampling strategies, and model fitting to data using evolutionary algorithms. The new research problems which cannot be directly deduced from the text mining data are also discussed

Nonlinear Control and Estimation of an Infammatory Immune Response

The immune response is a complex mechanism that can be triggered by biological or physical stresses on the organism. However an excessive and dys-regulated inflammatory response may lead to sepsis, a critical state, promoting tissue damage, organ dysfunction or even death.The main objective in this dissertation is to derive a strategy consisting of manipulating pro and anti-inflammatory mediators in order to direct the state of a virtual patient to a healthy equilibrium, after some disturbance from health due to infection. Two key challenges need to be addressed in solving such a problem: estimating the unmeasurable states of the inflammatory model as well as the model\u27s unknown rate parameters; and second, determining an appropriate strategy to effectively control the response.We initially study the nonlinear controllability, observability and identifiability of the inflammatory immune model. Then, we address the first challenge by comparing the performance of various nonlinear filters for state estimation in the presence of noise and incomplete information. For parameter estimation, a recently introduced approximate Markov chain Monte Carlo approach known as the Particle Metropolis- Hastings method is used. To control the highly nonlinear model, various model-based optimization approaches were investigated in which the control strategy is derived in terms of pro-inflammatory and anti-inflammatory response doses. Due to parameter variability and the difficult practical task of obtaining accurate state and parameter estimates in real time, a new model-free control methodology and its intelligent controllers is explored. The method does not rely on any precise modeling and the identification of each parameter of the inflammatory immune model is no longer needed for control design. The various methods are compared for performance to adequately control the responses in a diverse patient population as well as the clinical feasibility of the derived control protocol from the approach used

Optimal experimental design for parameter identification and model selection

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2014René Schenkendor