Direct sequential based firefly algorithm for the α-pinene isomerization problem

Publicado em: "Computational science and its applications – ICCSA 2016: 16th International Conference, Beijing, China, July 4-7, 2016, Proceedings, Part I"The problem herein addressed is a parameter estimation problem of the α-pinene process. The state variables of this bioengineering process satisfy a set of differential equations and depend on a set of unknown parameters. A dynamic system based parameter estimation problem aiming to estimate the model parameter values in a way that the predicted state variables best fit the experimentally observed state values is used. A numerical direct method, known as direct sequential procedure, is implemented giving rise to a finite bound constrained nonlinear optimization problem, which is solved by the metaheuristic firefly algorithm (FA). A Matlab programming environment is developed with the mathematical model and the computational application of the method. The results produced by FA, when compared to those of the fmincon function and other metaheuristics, are competitive.COMPETE: POCI-01- 0145-FEDER-007043FCT - Fundação para a Ciência e Tecnologia, within the projects UID/CEC/00319/2013 and UID/MAT/00013/201

DYNAMIC MATHEMATICAL TOOLS FOR THE IDENTIFICATION OF REGULATORY STRUCTURES AND KINETIC PARAMETERS IN

En aquesta tesi presentem una metodologia sistemàtica la qual permet caracteritzar sistemes biològics dinàmics a partir de dades de series temporals. Del treball desenvolupat se’n desprenen tres publicacions. En la primera desenvolupem un mètode d’optimització global determinista basat en l’outer approximation per a la estimació de paràmetres en sistemes biològics dinàmics. El nostre mètode es basa en la reformulació d’un conjunt d’equacions diferencials ordinàries al seu equivalent algebraic mitjançant l’ús de mètodes de col•locació ortogonal, donant lloc a un problema no convex programació no lineal (NLP). Aquest problema no convex NLP es descompon en dos nivells jeràrquics: un problema master de programació entera mixta (MILP) que proporciona una cota inferior rigorosa al solució global, i una NLP esclau d’espai reduït que dóna un límit superior. L’algorisme itera entre aquests dos nivells fins que un criteri de terminació es satisfà. En les publicacions segona i tercera vam desenvolupar un mètode que és capaç d’identificar l’estructura regulatòria amb els corresponents paràmetres cinètics a partir de dades de series temporals. En la segona publicació vam definir un problema d’optimització dinàmica entera mixta (MIDO) on minimitzem el criteri d’informació d’Akaike. En la tercera publicació vam adoptar una perspectiva MIDO multicriteri on minimitzem l’ajust i complexitat simultàniament mitjançant el mètode de l’epsilon constraint on un dels objectius es tracta com la funció objectiu mentre que la resta es converteixen en restriccions auxiliars. En ambdues publicacions els problemes MIDO es reformulen a programació entera mixta no lineal (MINLP) mitjançant la col•locació ortogonal en elements finits on les variables binàries s’utilitzem per modelar l’existència d’interaccions regulatòries.En esta tesis presentamos una metodología sistemática que permite caracterizar sistemas biológicos dinámicos a partir de datos de series temporales. Del trabajo desarrollado se desprenden tres publicaciones. En la primera desarrollamos un método de optimización global determinista basado en el outer approximation para la estimación de parámetros en sistemas biológicos dinámicos. Nuestro método se basa en la reformulación de un conjunto de ecuaciones diferenciales ordinarias a su equivalente algebraico mediante el uso de métodos de colocación ortogonal, dando lugar a un problema no convexo de programación no lineal (NLP). Este problema no convexo NLP se descompone en dos niveles jerárquicos: un problema master de programación entera mixta (MILP) que proporciona una cota inferior rigurosa al solución global, y una NLP esclavo de espacio reducido que da un límite superior. El algoritmo itera entre estos dos niveles hasta que un criterio de terminación se satisface. En las publicaciones segunda y tercera desarrollamos un método que es capaz de identificar la estructura regulatoria con los correspondientes parámetros cinéticos a partir de datos de series temporales. En la segunda publicación definimos un problema de optimización dinámica entera mixta (MIDO) donde minimizamos el criterio de información de Akaike. En la tercera publicación adoptamos una perspectiva MIDO multicriterio donde minimizamos el ajuste y complejidad simultáneamente mediante el método del epsilon constraint donde uno de los objetivos se trata como la función objetivo mientras que el resto se convierten en restricciones auxiliares. En ambas publicaciones los problemas MIDO se reformulan a programación entera mixta no lineal (MINLP) mediante la colocación ortogonal en elementos finitos donde las variables binarias se utilizan para modelar la existencia de interacciones regulatorias.In this thesis we present a systematic methodology to characterize dynamic biological systems from time series data. From the work we derived three publications. In the first we developed a deterministic global optimization method based on the outer approximation for parameter estimation in dynamic biological systems. Our method is based on reformulating the set of ordinary differential equations into an equivalent set of algebraic equations through the use of orthogonal collocation methods, giving rise to a nonconvex nonlinear programming (NLP) problem. This nonconvex NLP is decomposed into two hierarchical levels: a master mixed-integer linear programming problem (MILP) that provides a rigorous lower bound on the optimal solution, and a reduced-space slave NLP that yields an upper bound. The algorithm iterates between these two levels until a termination criterion is satisfied. In the second and third publications we developed a method that is able to identify the regulatory structure and its corresponding kinetic parameters from time series data. In the second publication we defined a mixed integer dynamic optimization problem (MIDO) which minimize the Akaike information criterion. In the third publication, we adopted a multi-criteria MIDO which minimize complexity and fit simultaneously using the epsilon constraint method in which one objective is treated as the objective function while the rest are converted to auxiliary constraints. In both publications MIDO problems were reformulated to mixed integer nonlinear programming (MINLP) through the use of orthogonal collocation on finite elements where binary variables are used to model the existence of regulatory interactions

Identification of metabolic system parameters using global optimization methods

BACKGROUND: The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. METHODS AND RESULTS: Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. CONCLUSION: The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks

Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

<p>Abstract</p> <p>Background</p> <p>Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements.</p> <p>Results</p> <p>We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in <it>Saccharomyces cerevisiae</it>. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast <it>Saccharomyces cerevisiae </it>to heat shock</p> <p>Conclusion</p> <p>Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.</p

Inference for Differential Equation Models using Relaxation via Dynamical Systems

Statistical regression models whose mean functions are represented by ordinary differential equations (ODEs) can be used to describe phenomenons dynamical in nature, which are abundant in areas such as biology, climatology and genetics. The estimation of parameters of ODE based models is essential for understanding its dynamics, but the lack of an analytical solution of the ODE makes the parameter estimation challenging. The aim of this paper is to propose a general and fast framework of statistical inference for ODE based models by relaxation of the underlying ODE system. Relaxation is achieved by a properly chosen numerical procedure, such as the Runge-Kutta, and by introducing additive Gaussian noises with small variances. Consequently, filtering methods can be applied to obtain the posterior distribution of the parameters in the Bayesian framework. The main advantage of the proposed method is computation speed. In a simulation study, the proposed method was at least 14 times faster than the other methods. Theoretical results which guarantee the convergence of the posterior of the approximated dynamical system to the posterior of true model are presented. Explicit expressions are given that relate the order and the mesh size of the Runge-Kutta procedure to the rate of convergence of the approximated posterior as a function of sample size

On metaheuristics for solving the parameter estimation problem in dynamic systems: A comparative study

This paper presents an experimental study that aims to compare the practical performance of well-known metaheuristics for solving the parameter estimation problem in a dynamic systems context. The metaheuristics produce good quality approximations to the global solution of a finite small-dimensional nonlinear programming problem that emerges from the application of the sequential numerical direct method to the parameter estimation problem. Using statistical hypotheses testing, significant differences in the performance of the metaheuristics, in terms of the average objective function values and average CPU time, are determined. Furthermore, the best obtained solutions are graphically compared in relative terms by means of the performance profiles. The numerical comparisons with other results in the literature show that the tested metaheuristics are effective in achieving good quality solutions with a reduced computational effort.The authors would like to acknowledge the financial support of CIDEM, R&D Unit, funded by the Portuguese Foundation for the Development of Science and Technology (FCT), Ministry of Science, Technology and Higher Education, under the Project UID/EMS/0615/2016, and of COMPETE: POCI-01-0145-FEDER-007043 and FCT within the Projects UID/CEC/00319/2013 and UID/MAT/00013/2013.info:eu-repo/semantics/publishedVersio

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