Dynamic Systems Biology Modeling and Simuation consolidates and unifies classical and contemporary multiscale methodologies for mathematical modeling and computer simulation of dynamic biological systems – from molecular/cellular, organ-system, on up to population levels. The book pedagogy is developed as a well-annotated, systematic tutorial – with clearly spelled-out and unified nomenclature – derived from the author’s own modeling efforts, publications and teaching over half a century. Ambiguities in some concepts and tools are clarified and others are rendered more accessible and practical. The latter include novel qualitative theory and methodologies for recognizing dynamical signatures in data using structural (multicompartmental and network) models and graph theory; and analyzing structural and measurement (data) models for quantification feasibility. The level is basic-to-intermediate, with much emphasis on biomodeling from real biodata, for use in real applications. Introductory coverage of core mathematical concepts such as linear and nonlinear differential and difference equations, Laplace transforms, linear algebra, probability, statistics and stochastics topics; PLUS ....... The pertinent biology, biochemistry, biophysics or pharmacology for modeling are provided, to support understanding the amalgam of “math modeling” with life sciences. Strong emphasis on quantifying as well as building and analyzing biomodels: includes methodology and computational tools for parameter identifiability and sensitivity analysis; parameter estimation from real data; model distinguishability and simplification; and practical bioexperiment design and optimization. Companion website provides solutions and program code for examples and exercises using Matlab, Simulink, VisSim, SimBiology, SAAMII, AMIGO, Copasi and SBML-coded models. A full set of PowerPoint slides are available from the author for teaching from his textbook. He uses them to teach a 10 week quarter upper division course at UCLA, which meets twice a week, so there are 20 lectures. They can easily be augmented or stretched for a 15 week semester course. Importantly, the slides are editable, so they can be readily adapted to a lecturer’s personal style and course content needs. The lectures are based on excerpts from 12 of the first 13 chapters of DSBMS. They are designed to highlight the key course material, as a study guide and structure for students following the full text content. The complete PowerPoint slide package (~25 MB) can be obtained by instructors (or prospective instructors) by emailing the author directly, at: [email protected]
Das Buch beschreibt die Grundlagen der mathematischen Modellierung zellulärer Systeme. Nach einer Klassifikation von Modellen wird schwerpunktmäßig auf deterministische Modelle eingegangen und für alle relevanten zellulären Prozesse entsprechende Gleichungen angegeben. Anschließend werden eine Reihe von Verfahren zur Modellanalyse vorgestellt. Etwas kürzer werden Verfahren zum Reverse Engineering und zur Analyse von Netzwerkgraphen abgehandelt. Am Ende werden noch Verfahren der Parameteridentifikation besprochen.
Systems techniques are integral to current research in molecular cell biology, and system-level investigations are often accompanied by mathematical models. These models serve as working hypotheses: they help us to understand and predict the behavior of complex systems. This book offers an introduction to mathematical concepts and techniques needed for the construction and interpretation of models in molecular systems biology. It is accessible to upper-level undergraduate or graduate students in life science or engineering who have some familiarity with calculus, and will be a useful reference for researchers at all levels. The first four chapters cover the basics of mathematical modeling in molecular systems biology. The last four chapters address specific biological domains, treating modeling of metabolic networks, of signal transduction pathways, of gene regulatory networks, and of electrophysiology and neuronal action potentials. Chapters 3--8 end with optional sections that address more specialized modeling topics. Exercises, solvable with pen-and-paper calculations, appear throughout the text to encourage interaction with the mathematical techniques. More involved end-of-chapter problem sets require computational software. Appendixes provide a review of basic concepts of molecular biology, additional mathematical background material, and tutorials for two computational software packages (XPPAUT and MATLAB) that can be used for model simulation and analysis.
Biophysical models have been used in biology for decades, but they have been limited in scope and size. In this book, Bernhard Ø. Palsson shows how network reconstructions that are based on genomic and bibliomic data, and take the form of established stoichiometric matrices, can be converted into dynamic models using metabolomic and fluxomic data. The Mass Action Stoichiometric Simulation (MASS) procedure can be used for any cellular process for which data is available and allows a scalable step-by-step approach to the practical construction of network models. Specifically, it can treat integrated processes that need explicit accounting of small molecules and protein, which allows simulation at the molecular level. The material has been class-tested by the author at both the undergraduate and graduate level. All computations in the text are available online in MATLAB and MATHEMATICA® workbooks, allowing hands-on practice with the material.
Since the first edition of Stochastic Modelling for Systems Biology, there have been many interesting developments in the use of "likelihood-free" methods of Bayesian inference for complex stochastic models. Re-written to reflect this modern perspective, this second edition covers everything necessary for a good appreciation of stochastic kinetic modelling of biological networks in the systems biology context. Keeping with the spirit of the first edition, all of the new theory is presented in a very informal and intuitive manner, keeping the text as accessible as possible to the widest possible readership. New in the Second Edition All examples have been updated to Systems Biology Markup Language Level 3 All code relating to simulation, analysis, and inference for stochastic kinetic models has been re-written and re-structured in a more modular way An ancillary website provides links, resources, errata, and up-to-date information on installation and use of the associated R package More background material on the theory of Markov processes and stochastic differential equations, providing more substance for mathematically inclined readers Discussion of some of the more advanced concepts relating to stochastic kinetic models, such as random time change representations, Kolmogorov equations, Fokker-Planck equations and the linear noise approximation Simple modelling of "extrinsic" and "intrinsic" noise An effective introduction to the area of stochastic modelling in computational systems biology, this new edition adds additional mathematical detail and computational methods that will provide a stronger foundation for the development of more advanced courses in stochastic biological modelling.
The emerging, multi-disciplinary field of systems biology is devoted to the study of the relationships between various parts of a biological system, and computer modeling plays a vital role in the drive to understand the processes of life from an holistic viewpoint. Advancements in experimental technologies in biology and medicine have generated an enormous amount of biological data on the dependencies and interactions of many different molecular cell processes, fueling the development of numerous computational methods for exploring this data. The mathematical formalism of Petri net theory is able to encompass many of these techniques. This essential text/reference presents a comprehensive overview of cutting-edge research in applications of Petri nets in systems biology, with contributions from an international selection of experts. Those unfamiliar with the field are also provided with a general introduction to systems biology, the foundations of biochemistry, and the basics of Petri net theory. Further chapters address Petri net modeling techniques for building and analyzing biological models, as well as network prediction approaches, before reviewing the applications to networks of different biological classification. Topics and features: investigates the modular, qualitative modeling of regulatory networks using Petri nets, and examines an Hybrid Functional Petri net simulation case study; contains a glossary of the concepts and notation used in the book, in addition to exercises at the end of each chapter; covers the topological analysis of metabolic and regulatory networks, the analysis of models of signaling networks, and the prediction of network structure; provides a biological case study on the conversion of logical networks into Petri nets; discusses discrete modeling, stochastic modeling, fuzzy modeling, dynamic pathway modeling, genetic regulatory network modeling, and quantitative analysis techniques; includes a Foreword by Professor Jens Reich, Professor of Bioinformatics at Humboldt University and Max Delbrück Center for Molecular Medicine in Berlin. This unique guide to the modeling of biochemical systems using Petri net concepts will be of real utility to researchers and students of computational biology, systems biology, bioinformatics, computer science, and biochemistry.
Systems biology is changing the way biological systems are studied by allowing us to examine the cell and organism as a whole. Systems biotechnology allows optimal design and development of upstream to downstream bioprocesses by taking a systems-approach. E. coli has been a model organism for almost all biological and biotechnological studies. This book brings together for the first time the state-of-the-art reviews by the world-leading experts on systems biology and biotechnological applications of E. coli. The topics covered include genomics and functional genomics, resources for systems biology, network analysis, genome-scale metabolic reconstruction, modelling and simulation, dynamic modelling and simulation, systems-level analysis of evolution, plasmids and expression systems, protein synthesis, production and export, engineering the central metabolism, synthetic biology, and systems metabolic engineering of E. coli. This book provides readers with guidance on how a complex biological system can be studied using E. coli as a model organism. It also presents how to perform synthetic biology and systems metabolic engineering studies on E. coli with successful examples, the approaches of which can be extended to other organisms. This book will be a complete resource for anyone interested in systems biology and biotechnology.
Stochastic kinetic methods are currently considered to be the most realistic and elegant means of representing and simulating the dynamics of biochemical and biological networks. Deterministic versus stochastic modelling in biochemistry and systems biology introduces and critically reviews the deterministic and stochastic foundations of biochemical kinetics, covering applied stochastic process theory for application in the field of modelling and simulation of biological processes at the molecular scale. Following an overview of deterministic chemical kinetics and the stochastic approach to biochemical kinetics, the book goes onto discuss the specifics of stochastic simulation algorithms, modelling in systems biology and the structure of biochemical models. Later chapters cover reaction-diffusion systems, and provide an analysis of the Kinfer and BlenX software systems. The final chapter looks at simulation of ecodynamics and food web dynamics. Introduces mathematical concepts and formalisms of deterministic and stochastic modelling through clear and simple examples Presents recently developed discrete stochastic formalisms for modelling biological systems and processes Describes and applies stochastic simulation algorithms to implement a stochastic formulation of biochemical and biological kinetics
With more and more interest in how components of biological systems interact, it is important to understand the various aspects of systems biology. Kinetic Modelling in Systems Biology focuses on one of the main pillars in the future development of systems biology. It explores both the methods and applications of kinetic modeling in this emerging field. The book introduces the basic biological cellular network concepts in the context of cellular functioning, explains the main aspects of the Edinburgh Pathway Editor (EPE) software package, and discusses the process of constructing and verifying kinetic models. It presents the features, user interface, and examples of DBSolve as well as the principles of modeling individual enzymes and transporters. The authors describe how to construct kinetic models of intracellular systems on the basis of models of individual enzymes. They also illustrate how to apply the principles of kinetic modeling to collect all available information on the energy metabolism of whole organelles, construct a kinetic model, and predict the response of the organelle to changes in external conditions. The final chapter focuses on applications of kinetic modeling in biotechnology and biomedicine. Encouraging readers to think about future challenges, this book will help them understand the kinetic modeling approach and how to apply it to solve real-life problems. CD-ROM Features Extensively used throughout the text for pathway visualization and illustration, the EPE software is available on the accompanying CD-ROM. The CD also includes pathway diagrams in several graphical formats, DBSolve installation with examples, and all models from the book with dynamic visualization of simulation results, allowing readers to perform in silico simulations and use the models as templates for further applications.
For life to be understood and disease to become manageable, the wealth of postgenomic data now needs to be made dynamic. This development requires systems biology, integrating computational models for cells and organisms in health and disease; quantitative experiments (high-throughput, genome-wide, living cell, in silico); and new concepts and principles concerning interactions. This book defines the new field of systems biology and discusses the most efficient experimental and computational strategies. The benefits for industry, such as the new network-based drug-target design validation, and testing, are also presented.
From controlling disease outbreaks to predicting heart attacks, dynamic models are increasingly crucial for understanding biological processes. Many universities are starting undergraduate programs in computational biology to introduce students to this rapidly growing field. In Dynamic Models in Biology, the first text on dynamic models specifically written for undergraduate students in the biological sciences, ecologist Stephen Ellner and mathematician John Guckenheimer teach students how to understand, build, and use dynamic models in biology. Developed from a course taught by Ellner and Guckenheimer at Cornell University, the book is organized around biological applications, with mathematics and computing developed through case studies at the molecular, cellular, and population levels. The authors cover both simple analytic models--the sort usually found in mathematical biology texts--and the complex computational models now used by both biologists and mathematicians. Linked to a Web site with computer-lab materials and exercises, Dynamic Models in Biology is a major new introduction to dynamic models for students in the biological sciences, mathematics, and engineering.
A unique, hands-on guide to interactive modeling andsimulation of engineering systems This book describes advanced, cutting-edge techniques fordynamic system simulation using the DESIRE modeling/simulationsoftware package. It offers detailed guidance on how to implementthe software, providing scientists and engineers with powerfultools for creating simulation scenarios and experiments for suchdynamic systems as aerospace vehicles, control systems, orbiological systems. Along with two new chapters on neural networks, AdvancedDynamic-System Simulation, Second Edition revamps and updatesall the material, clarifying explanations and adding many newexamples. A bundled CD contains an industrial-strength version ofOPEN DESIRE as well as hundreds of program examples that readerscan use in their own experiments. The only book on the market todemonstrate model replication and Monte Carlo simulation ofreal-world engineering systems, this volume: Presents a newly revised systematic procedure fordifference-equation modeling Covers runtime vector compilation for fast model replication ona personal computer Discusses parameter-influence studies, introducing very fastvectorized statistics computation Highlights Monte Carlo studies of the effects of noise andmanufacturing tolerances for control-system modeling Demonstrates fast, compact vector models of neural networks forcontrol engineering Features vectorized programs for fuzzy-set controllers, partialdifferential equations, and agro-ecological modeling Advanced Dynamic-System Simulation, Second Edition is atruly useful resource for researchers and design engineers incontrol and aerospace engineering, ecology, and agriculturalplanning. It is also an excellent guide for students usingDESIRE.
This advanced textbook is tailored for an introductory course in Systems Biology and is well-suited for biologists as well as engineers and computer scientists. It comes with student-friendly reading lists and a companion website featuring a short exam prep version of the book and educational modeling programs. The text is written in an easily accessible style and includes numerous worked examples and study questions in each chapter. For this edition, a section on medical systems biology has been included.
The development and use of models of various objects is becoming a more common practice in recent days. This is due to the ease with which models can be developed and examined through the use of computers and appropriate software. Of those two, the former - high-speed computers - are easily accessible nowadays, and the latter - existing programs - are being updated almost continuously, and at the same time new powerful software is being developed. Usually a model represents correlations between some processes and their interactions, with better or worse quality of representation. It details and characterizes a part of the real world taking into account a structure of phenomena, as well as quantitative and qualitative relations. There are a great variety of models. Modelling is carried out in many diverse fields. All types of natural phenomena in the area of biology, ecology and medicine are possible subjects for modelling. Models stand for and represent technical objects in physics, chemistry, engineering, social events and behaviours in sociology, financial matters, investments and stock markets in economy, strategy and tactics, defence, security and safety in military fields. There is one common point for all models. We expect them to fulfil the validity of prediction. It means that through the analysis of models it is possible to predict phenomena, which may occur in a fragment of the real world represented by a given model. We also expect to be able to predict future reactions to signals from the outside world.
This book provides an introductory text for undergraduate and graduate students who are interested in comprehensive biological systems. The authors offer a broad overview of the field using key examples and typical approaches to experimental design. The volume begins with an introduction to systems biology and then details experimental omics tools. Other sections introduce the reader to challenging computational approaches. The final sections provide ideas for theoretical and modeling optimization in systemic biological researches. The book is an indispensable resource, providing a first glimpse into the state-of-the-art in systems biology.
Simulation is increasingly important for students in a wide variety of fields, from engineering and physical sciences to medicine, biology, economics, and applied mathematics. Current trends point toward interdisciplinary courses in simulation intended for all students regardless of their major, but most textbooks are subject-specific and consequently are not suitable for such a course. Simulation of Dynamic Systems with MATLAB® and Simulink® offers a unified introduction to continuous simulation that focuses on the common principles underlying the vast array of simulation models that describe very different phenomena. Written by accomplished expert Harold Klee, this text builds an in-depth and intuitive understanding of the basic concepts and mathematical tools that students can easily generalize to their own field of study. The author includes case studies, real-world examples, abundant homework problems, and thousands of equations to develop a practical understanding of the concepts. Moreover, he incorporates MATLAB® and Simulink® tools to help students gain experience with designing, implementing, and adjusting their simulations. This classroom-tested text works systematically through linear, continuous-time, and discrete-time dynamic systems as well as basic, intermediate, and advanced topics in numerical integration. Supplying downloadable MATLAB M-files and Simulink model files, Simulation of Dynamic Systems with MATLAB® and Simulink® is ideal for a one- or two-semester course in continuous simulation, offering valuable flexibility for instructors.
Author: P. P. J. van den Bosch,A. C. van der Klauw
Publisher: CRC Press
Category: Technology & Engineering
This book gives an in-depth introduction to the areas of modeling, identification, simulation, and optimization. These scientific topics play an increasingly dominant part in many engineering areas such as electrotechnology, mechanical engineering, aerospace, and physics. This book represents a unique and concise treatment of the mutual interactions among these topics. Techniques for solving general nonlinear optimization problems as they arise in identification and many synthesis and design methods are detailed. The main points in deriving mathematical models via prior knowledge concerning the physics describing a system are emphasized. Several chapters discuss the identification of black-box models. Simulation is introduced as a numerical tool for calculating time responses of almost any mathematical model. The last chapter covers optimization, a generally applicable tool for formulating and solving many engineering problems.
This comprehensively revised second edition of Computational Systems Biology discusses the experimental and theoretical foundations of the function of biological systems at the molecular, cellular or organismal level over temporal and spatial scales, as systems biology advances to provide clinical solutions to complex medical problems. In particular the work focuses on the engineering of biological systems and network modeling. Logical information flow aids understanding of basic building blocks of life through disease phenotypes Evolved principles gives insight into underlying organizational principles of biological organizations, and systems processes, governing functions such as adaptation or response patterns Coverage of technical tools and systems helps researchers to understand and resolve specific systems biology problems using advanced computation Multi-scale modeling on disparate scales aids researchers understanding of dependencies and constraints of spatio-temporal relationships fundamental to biological organization and function.
Corrado Priami,INTERNATIONAL WORKSHOP ON COMPUTATIONAL METHODS IN,International Workshop on Computational Methods in Systems Biology 200
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