Verification of system properties of polynomial systems using discrete-time approximations and set-based analysis

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2015von Philipp Rumschinsk

ADMIT: a toolbox for guaranteed model invalidation, estimation and qualitative–quantitative modeling

Summary: Often competing hypotheses for biochemical networks exist in the form of different mathematical models with unknown parameters. Considering available experimental data, it is then desired to reject model hypotheses that are inconsistent with the data, or to estimate the unknown parameters. However, these tasks are complicated because experimental data are typically sparse, uncertain, and are frequently only available in form of qualitative if–then observations. ADMIT (Analysis, Design and Model Invalidation Toolbox) is a MatLabTM-based tool for guaranteed model invalidation, state and parameter estimation. The toolbox allows the integration of quantitative measurement data, a priori knowledge of parameters and states, and qualitative information on the dynamic or steady-state behavior. A constraint satisfaction problem is automatically generated and algorithms are implemented for solving the desired estimation, invalidation or analysis tasks. The implemented methods built on convex relaxation and optimization and therefore provide guaranteed estimation results and certificates for invalidity

ADMIT: a toolbox for guaranteed model invalidation, estimation and qualitative–quantitative modeling

Summary: Often competing hypotheses for biochemical networks exist in the form of different mathematical models with unknown parameters. Considering available experimental data, it is then desired to reject model hypotheses that are inconsistent with the data, or to estimate the unknown parameters. However, these tasks are complicated because experimental data are typically sparse, uncertain, and are frequently only available in form of qualitative if–then observations. ADMIT (Analysis, Design and Model Invalidation Toolbox) is a MatLabTM-based tool for guaranteed model invalidation, state and parameter estimation. The toolbox allows the integration of quantitative measurement data, a priori knowledge of parameters and states, and qualitative information on the dynamic or steady-state behavior. A constraint satisfaction problem is automatically generated and algorithms are implemented for solving the desired estimation, invalidation or analysis tasks. The implemented methods built on convex relaxation and optimization and therefore provide guaranteed estimation results and certificates for invalidity

Fault Diagnosis for Polynomial Hybrid Systems

Safety requirements of technological processes trigger an increased demand for elaborate fault diagnosis tools. However, abrupt changes in system behavior are hard to formulate with continuous models but easier to represent in terms of hybrid systems. Therefore, we propose a set-based approach for complete fault diagnosis of hybrid polynomial systems formulated as a feasibility problem. We employ mixed-integer linear program relaxation of this formulation to exploit the presence of discrete variables. We improve the relaxation with additional constraints for the discrete variables. The efficiency of the method is illustrated with a simple two-tank example subject to multiple faults

Set-base dynamical parameter estimation and model invalidation for biochemical reaction networks

<p>Abstract</p> <p>Background</p> <p>Mathematical modeling and analysis have become, for the study of biological and cellular processes, an important complement to experimental research. However, the structural and quantitative knowledge available for such processes is frequently limited, and measurements are often subject to inherent and possibly large uncertainties. This results in competing model hypotheses, whose kinetic parameters may not be experimentally determinable. Discriminating among these alternatives and estimating their kinetic parameters is crucial to improve the understanding of the considered process, and to benefit from the analytical tools at hand.</p> <p>Results</p> <p>In this work we present a set-based framework that allows to discriminate between competing model hypotheses and to provide guaranteed outer estimates on the model parameters that are consistent with the (possibly sparse and uncertain) experimental measurements. This is obtained by means of exact proofs of model invalidity that exploit the polynomial/rational structure of biochemical reaction networks, and by making use of an efficient strategy to balance solution accuracy and computational effort.</p> <p>Conclusions</p> <p>The practicability of our approach is illustrated with two case studies. The first study shows that our approach allows to conclusively rule out wrong model hypotheses. The second study focuses on parameter estimation, and shows that the proposed method allows to evaluate the global influence of measurement sparsity, uncertainty, and prior knowledge on the parameter estimates. This can help in designing further experiments leading to improved parameter estimates.</p

Graph problems arising from parameter identification of discrete dynamical systems

This paper focuses on combinatorial feasibility and optimization problems that arise in the context of parameter identification of discrete dynamical systems. Given a candidate parametric model for a physical system and a set of experimental observations, the objective of parameter identification is to provide estimates of the parameter values for which the model can reproduce the experiments. To this end, we define a finite graph corresponding to the model, to each arc of which a set of parameters is associated. Paths in this graph are regarded as feasible only if the sets of parameters corresponding to the arcs of the path have nonempty intersection. We study feasibility and optimization problems on such feasible paths, focusing on computational complexity. We show that, under certain restrictions on the sets of parameters, some of the problems become tractable, whereas others are NP-hard. In a similar vein, we define and study some graph problems for experimental design, whose goal is to support the scientist in optimally designing new experiment

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