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.

This monograph has the ambitious aim of developing a mathematical theory of complex biological systems with special attention to the phenomena of ageing, degeneration and repair of biological tissues under individual self-repair actions that may have good potential in medical therapy. The approach to mathematically modeling biological systems needs to tackle the additional difficulties generated by the peculiarities of living matter. These include the lack of invariance principles, abilities to express strategies for individual fitness, heterogeneous behaviors, competition up to proliferative and/or destructive actions, mutations, learning ability, evolution and many others. Applied mathematicians in the field of living systems, especially biological systems, will appreciate the special class of integro-differential equations offered here for modeling at the molecular, celular and tissue scales. A unique perspective is also presented with a number of case studies in biological modeling.

This book develops the mathematical tools essential for students in the life sciences to describe interacting systems and predict their behavior. From predator-prey populations in an ecosystem, to hormone regulation within the body, the natural world abounds in dynamical systems that affect us profoundly. Complex feedback relations and counter-intuitive responses are common in nature; this book develops the quantitative skills needed to explore these interactions. Differential equations are the natural mathematical tool for quantifying change, and are the driving force throughout this book. The use of Euler’s method makes nonlinear examples tractable and accessible to a broad spectrum of early-stage undergraduates, thus providing a practical alternative to the procedural approach of a traditional Calculus curriculum. Tools are developed within numerous, relevant examples, with an emphasis on the construction, evaluation, and interpretation of mathematical models throughout. Encountering these concepts in context, students learn not only quantitative techniques, but how to bridge between biological and mathematical ways of thinking. Examples range broadly, exploring the dynamics of neurons and the immune system, through to population dynamics and the Google PageRank algorithm. Each scenario relies only on an interest in the natural world; no biological expertise is assumed of student or instructor. Building on a single prerequisite of Precalculus, the book suits a two-quarter sequence for first or second year undergraduates, and meets the mathematical requirements of medical school entry. The later material provides opportunities for more advanced students in both mathematics and life sciences to revisit theoretical knowledge in a rich, real-world framework. In all cases, the focus is clear: how does the math help us understand the science?

Volume II of this two-volume, interdisciplinary work is a unified presentation of a broad range of state-of-the-art topics in the rapidly growing field of mathematical modeling in the biological sciences. Highlighted throughout are mathematical and computational apporaches to examine central problems in the life sciences, ranging from the organization principles of individual cells to the dynamics of large populations. The chapters are thematically organized into the following main areas: epidemiology, evolution and ecology, immunology, neural systems and the brain, and innovative mathematical methods and education. The work will be an excellent reference text for a broad audience of researchers, practitioners, and advanced students in this rapidly growing field at the intersection of applied mathematics, experimental biology and medicine, computational biology, biochemistry, computer science, and physics.

This book describes the evolution of several socio-biological systems using mathematical kinetic theory. Specifically, it deals with modeling and simulations of biological systems whose dynamics follow the rules of mechanics as well as rules governed by their own ability to organize movement and biological functions. It proposes a new biological model focused on the analysis of competition between cells of an aggressive host and cells of a corresponding immune system. Proposed models are related to the generalized Boltzmann equation. The book may be used for advanced graduate courses and seminars in biological systems modeling.

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.

This book developed from classes in mathematical biology taught by the authors over several years at the Technische Universität München. The main themes are modeling principles, mathematical principles for the analysis of these models and model-based analysis of data. The key topics of modern biomathematics are covered: ecology, epidemiology, biochemistry, regulatory networks, neuronal networks and population genetics. A variety of mathematical methods are introduced, ranging from ordinary and partial differential equations to stochastic graph theory and branching processes. A special emphasis is placed on the interplay between stochastic and deterministic models.