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: firstname.lastname@example.org
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.
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.
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.
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.
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
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.
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.
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.
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.
This book explores Systems Biology as the understanding of biological network behaviors, and in particular their dynamic aspects, which requires the utilization of mathematical modeling tightly linked to experiment. A variety of approaches are discussed here: the identification and validation of networks, the creation of appropriate datasets, the development of tools for data acquisition and software development, and the use of modeling and simulation software in close concert with experiment.
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.
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.
Computer Simulation Analysis of Biological and Agricultural Systems focuses on the integration of mathematical models and the dynamic simulation essential to system analysis, design, and synthesis. The book emphasizes the quantitative dynamic relationships between elements and system responses. Problems of various degrees of difficulty and complexity are discussed to illustrate methods of computer-aided design and analysis that can bridge the gap between theories and applications. These problems cover a wide variety of subjects in the biological and agricultural fields. Specific guidelines and practical methods for defining requirements, developing specifications, and integrating system modeling early in simulation development are included as well. Computer Simulation Analysis of Biological and Agricultural Systems is an excellent text and self-guide for agricultural engineers, agronomists, foresters, horticulturists, soil scientists, mechanical engineers, and computer simulators.
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.
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.
Model-replication Techniques and Monte Carlo Simulation
Author: Granino A. Korn
Publisher: John Wiley & Sons
Learn the latest techniques in programming sophisticated simulation systems This cutting-edge text presents the latest techniques in advanced simulation programming for interactive modeling and simulation of dynamic systems, such as aerospace vehicles, control systems, and biological systems. The author, a leading authority in the field, demonstrates computer software that can handle large simulation studies on standard personal computers. Readers can run, edit, and modify the sample simulations from the text with the accompanying CD-ROM, featuring the OPEN DESIRE program for Linux and Windows. The program included on CD solves up to 40,000 ordinary differential equations and implements exceptionally fast and convenient vector operations. The text begins with an introduction to dynamic-system simulation, including a demonstration of a simple guided-missile simulation. Among the other highlights of coverage are: Models that involve sampled-data operations and sampled-data difference equations, including improved techniques for proper numerical integration of switched variables Novel vector compiler that produces exceptionally fast programs for vector and matrix assignments, differential equations, and difference equations Application of vector compiler to parameter-influence studies and Monte Carlo simulation of dynamic systems Vectorized Monte Carlo simulations involving time-varying noise, derived from periodic pseudorandom-noise samples Vector models of neural networks, including a new pulsed-neuron model Vectorized programs for fuzzy-set controller, partial differential equations, and agro-ecological models replicated at many points of a landscape map This text is intended for graduate-level students, engineers, and computer scientists, particularly those involved in aerospace, control system design, chemical process control, and biological systems. All readers will gain the practical skills they need to design sophisticated simulations of dynamic systems. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.
From the spontaneous rapid firing of cortical neurons to the spatial diffusion of disease epidemics, biological systems exhibit rich dynamic behaviour over a vast range of time and space scales. Unifying many of these diverse phenomena, Dynamics of Biological Systems provides the computational and mathematical platform from which to understand the underlying processes of the phenomena. Through an extensive tour of various biological systems, the text introduces computational methods for simulating spatial diffusion processes in excitable media, such as the human heart, as well as mathematical tools for dealing with systems of nonlinear ordinary and partial differential equations, such as neuronal activation and disease diffusion. The mathematical models and computer simulations offer insight into the dynamics of temporal and spatial biological systems, including cardiac pacemakers, artificial electrical defibrillation, pandemics, pattern formation, flocking behaviour, the interaction of autonomous agents, and hierarchical and structured network topologies. Tools from complex systems and complex networks are also presented for dealing with real phenomenological systems. With exercises and projects in each chapter, this classroom-tested text shows students how to apply a variety of mathematical and computational techniques to model and analyze the temporal and spatial phenomena of biological systems. MATLAB® implementations of algorithms and case studies are available on the author’s website.
This book is intended as a text for a first course on creating and analyzing computer simulation models of biological systems. The expected audience for this book are students wishing to use dynamic models to interpret real data mueh as they would use standard statistical techniques. It is meant to provide both the essential principles as well as the details and equa tions applicable to a few particular systems and subdisciplines. Biological systems, however, encompass a vast, diverse array of topics and problems. This book discusses only a select number of these that I have found to be useful and interesting to biologists just beginning their appreciation of computer simulation. The examples chosen span classical mathematical models of well-studied systems to state-of-the-art topics such as cellular automata and artificial life. I have stressed the relationship between the models and the biology over mathematical analysis in order to give the reader a sense that mathematical models really are useful to biologists. In this light, I have sought examples that address fundamental and, I think, interesting biological questions. Almost all of the models are directly COIIl pared to quantitative data to provide at least a partial demonstration that some biological models can accurately predict.