An introduction and overview of system modeling in biology that is accessible to researchers from different fields, including biology, computer science, mathematics, statistics, physics, and biochemistry.

This textbook contains the essential knowledge in modeling, simulation, analysis, and applications in dealing with biological cellular control systems. In particular, the book shows how to use the law of mass balance and the law of mass action to derive an enzyme kinetic model - the Michaelis-Menten function or the Hill function, how to use a current-voltage relation, Nernst potential equilibrium equation, and Hodgkin and Huxley's models to model an ionic channel or pump, and how to use the law of mass balance to integrate these enzyme or channel models into a complete feedback control system. The book also illustrates how to use data to estimate parameters in a model, how to use MATLAB to solve a model numerically, how to do computer simulations, and how to provide model predictions. Furthermore, the book demonstrates how to conduct a stability and sensitivity analysis on a model.

An introduction to the mathematical concepts and techniques needed for the construction and analysis of models in molecular systems biology. 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.

How can we understand the complexity of genes, RNAs, and proteins and the associated regulatory networks? One approach is to look for recurring types of dynamical behavior. Mathematical models prove to be useful, especially models coming from theories of biochemical reactions such as ordinary differential equation models. Clever, careful experiments test these models and their basis in specific theories. This textbook aims to provide advanced students with the tools and insights needed to carry out studies of signal transduction drawing on modeling, theory, and experimentation. Early chapters summarize the basic building blocks of signaling systems: binding/dissociation, synthesis/destruction, and activation/inactivation. Subsequent chapters introduce various basic circuit devices: amplifiers, stabilizers, pulse generators, switches, stochastic spike generators, and oscillators. All chapters consistently use approaches and concepts from chemical kinetics and nonlinear dynamics, including rate-balance analysis, phase plane analysis, nullclines, linear stability analysis, stable nodes, saddles, unstable nodes, stable and unstable spirals, and bifurcations. This textbook seeks to provide quantitatively inclined biologists and biologically inclined physicists with the tools and insights needed to apply modeling and theory to interesting biological processes. Key Features: Full-color illustration program with diagrams to help illuminate the concepts Enables the reader to apply modeling and theory to the biological processes Further Reading for each chapter High-quality figures available for instructors to download

An introduction and overview of system modeling in biology that is accessible to researchers from different fields, including biology, computer science, mathematics, statistics, physics, and biochemistry. Research in systems biology requires the collaboration of researchers from diverse backgrounds, including biology, computer science, mathematics, statistics, physics, and biochemistry. These collaborations, necessary because of the enormous breadth of background needed for research in this field, can be hindered by differing understandings of the limitations and applicability of techniques and concerns from different disciplines. This comprehensive introduction and overview of system modeling in biology makes the relevant background material from all pertinent fields accessible to researchers with different backgrounds. The emerging area of systems level modeling in cellular biology has lacked a critical and thorough overview. This book fills that gap. It is the first to provide the necessary critical comparison of concepts and approaches, with an emphasis on their possible applications. It presents key concepts and their theoretical background, including the concepts of robustness and modularity and their exploitation to study biological systems; the best-known modeling approaches, and their advantages and disadvantages; lessons from the application of mathematical models to the study of cellular biology; and available modeling tools and datasets, along with their computational limitations.

The dynamic development of various processes is a central problem of biology and indeed of all the sciences. The mathematics describing that development is, in general, complicated, because the models that are realistic are usually nonlinear. Consequently many biologists may not notice a possible application of theory. They may be unable to decide whether a particular model captures the essence of a system, or to appreciate that analysis of a model can reveal important aspects of biological problems and may even describe in detail how a system works. The aim of this textbook is to remedy the situation by adopting a general approach to model analysis and applying it several times to problems (drawn primarily from molecular and cellular biology) of gradually increasing biological and mathematical complexity. Although material of considerable sophistication is included, little mathematical background is required - only some exposure to elementary calculus; appendixes supply the necessary mathematics and the author concentrates on concepts rather than techniques. He also emphasizes the role of computers in giving a full picture of model behavior and complementing more qualitative analysis. Some problems suitable for computer analysis are also included. This is a class-tested textbook suitable for a one-semester course for advanced undergraduate and beginning graduate students in biology or applied mathematics. It can also be used as a source book for teachers and a reference for specialists.

Models help us understand the dynamics of real-world processes by using the computer to mimic the actual forces that are known or assumed to result in a system's behavior. This book does not require a substantial background in mathematics or computer science.

What every neuroscientist should know about the mathematical modeling of excitable cells, presented at an introductory level.

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.

Drawing on the latest research in the field, Systems Biology: Mathematical Modeling and Model Analysis presents many methods for modeling and analyzing biological systems, in particular cellular systems. It shows how to use predictive mathematical models to acquire and analyze knowledge about cellular systems. It also explores how the models are systematically applied in biotechnology. The first part of the book introduces biological basics, such as metabolism, signaling, gene expression, and control as well as mathematical modeling fundamentals, including deterministic models and thermodynamics. The text also discusses linear regression methods, explains the differences between linear and nonlinear regression, and illustrates how to determine input variables to improve estimation accuracy during experimental design. The second part covers intracellular processes, including enzymatic reactions, polymerization processes, and signal transduction. The author highlights the process–function–behavior sequence in cells and shows how modeling and analysis of signal transduction units play a mediating role between process and function. The third part presents theoretical methods that address the dynamics of subsystems and the behavior near a steady state. It covers techniques for determining different time scales, sensitivity analysis, structural kinetic modeling, and theoretical control engineering aspects, including a method for robust control. It also explores frequent patterns (motifs) in biochemical networks, such as the feed-forward loop in the transcriptional network of E. coli. Moving on to models that describe a large number of individual reactions, the last part looks at how these cellular models are used in biotechnology. The book also explains how graphs can illustrate the link between two components in large networks with several interactions.