This book focuses on counting processes and continuous-time Markov chains motivated by examples and applications drawn from chemical networks in systems biology. The book should serve well as a supplement for courses in probability and stochastic processes. While the material is presented in a manner most suitable for students who have studied stochastic processes up to and including martingales in continuous time, much of the necessary background material is summarized in the Appendix. Students and Researchers with a solid understanding of calculus, differential equations and elementary probability and who are well-motivated by the applications will find this book of interest. David F. Anderson is Associate Professor in the Department of Mathematics at the University of Wisconsin and Thomas G. Kurtz is Emeritus Professor in the Departments of Mathematics and Statistics at that university. Their research is focused on probability and stochastic processes with applications in biology and other areas of science and technology. These notes are based in part on lectures given by Professor Anderson at the University of Wisconsin – Madison and by Professor Kurtz at Goethe University Frankfurt.
This textbook focuses on stochastic analysis in systems biology containing both the theory and application. While the authors provide a review of probability and random variables, subsequent notions of biochemical reaction systems and the relevant concepts of probability theory are introduced side by side. This leads to an intuitive and easy-to-follow presentation of stochastic framework for modeling subcellular biochemical systems. In particular, the authors make an effort to show how the notion of propensity, the chemical master equation and the stochastic simulation algorithm arise as consequences of the Markov property. The text contains many illustrations, examples and exercises to illustrate the ideas and methods that are introduced. Matlab code is also provided where appropriate. Additionally, the cell cycle is introduced as a more complex case study. Senior undergraduate and graduate students in mathematics and physics as well as researchers working in the area of systems biology, bioinformatics and related areas will find this text useful.
This book provides an introduction to the analysis of stochastic dynamic models in biology and medicine. The main aim is to offer a coherent set of probabilistic techniques and mathematical tools which can be used for the simulation and analysis of various biological phenomena. These tools are illustrated on a number of examples. For each example, the biological background is described, and mathematical models are developed following a unified set of principles. These models are then analyzed and, finally, the biological implications of the mathematical results are interpreted. The biological topics covered include gene expression, biochemistry, cellular regulation, and cancer biology. The book will be accessible to graduate students who have a strong background in differential equations, the theory of nonlinear dynamical systems, Markovian stochastic processes, and both discrete and continuous state spaces, and who are familiar with the basic concepts of probability theory.
This book develops the theory of continuous and discrete stochastic processes within the context of cell biology. In the second edition the material has been significantly expanded, particularly within the context of nonequilibrium and self-organizing systems. Given the amount of additional material, the book has been divided into two volumes, with volume I mainly covering molecular processes and volume II focusing on cellular processes. A wide range of biological topics are covered in the new edition, including stochastic ion channels and excitable systems, molecular motors, stochastic gene networks, genetic switches and oscillators, epigenetics, normal and anomalous diffusion in complex cellular environments, stochastically-gated diffusion, active intracellular transport, signal transduction, cell sensing, bacterial chemotaxis, intracellular pattern formation, cell polarization, cell mechanics, biological polymers and membranes, nuclear structure and dynamics, biological condensates, molecular aggregation and nucleation, cellular length control, cell mitosis, cell motility, cell adhesion, cytoneme-based morphogenesis, bacterial growth, and quorum sensing. The book also provides a pedagogical introduction to the theory of stochastic and nonequilibrium processes – Fokker Planck equations, stochastic differential equations, stochastic calculus, master equations and jump Markov processes, birth-death processes, Poisson processes, first passage time problems, stochastic hybrid systems, queuing and renewal theory, narrow capture and escape, extreme statistics, search processes and stochastic resetting, exclusion processes, WKB methods, large deviation theory, path integrals, martingales and branching processes, numerical methods, linear response theory, phase separation, fluctuation-dissipation theorems, age-structured models, and statistical field theory. This text is primarily aimed at graduate students and researchers working in mathematical biology, statistical and biological physicists, and applied mathematicians interested in stochastic modeling. Applied probabilists should also find it of interest. It provides significant background material in applied mathematics and statistical physics, and introduces concepts in stochastic and nonequilibrium processes via motivating biological applications. The book is highly illustrated and contains a large number of examples and exercises that further develop the models and ideas in the body of the text. It is based on a course that the author has taught at the University of Utah for many years.
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
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. Having been thoroughly updated to reflect this, this third edition covers everything necessary for a good appreciation of stochastic kinetic modelling of biological networks in the systems biology context. New methods and applications are included in the book, and the use of R for practical illustration of the algorithms has been greatly extended. There is a brand new chapter on spatially extended systems, and the statistical inference chapter has also been extended with new methods, including approximate Bayesian computation (ABC). Stochastic Modelling for Systems Biology, Third Edition is now supplemented by an additional software library, written in Scala, described in a new appendix to the book. New in the Third Edition New chapter on spatially extended systems, covering the spatial Gillespie algorithm for reaction diffusion master equation models in 1- and 2-d, along with fast approximations based on the spatial chemical Langevin equation Significantly expanded chapter on inference for stochastic kinetic models from data, covering ABC, including ABC-SMC Updated R package, including code relating to all of the new material New R package for parsing SBML models into simulatable stochastic Petri net models New open-source software library, written in Scala, replicating most of the functionality of the R packages in a fast, compiled, strongly typed, functional language Keeping with the spirit of earlier editions, 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. An effective introduction to the area of stochastic modelling in computational systems biology, this new edition adds additional detail and computational methods that will provide a stronger foundation for the development of more advanced courses in stochastic biological modelling.
Stochastic Models in Biology describes the usefulness of the theory of stochastic process in studying biological phenomena. The book describes analysis of biological systems and experiments though probabilistic models rather than deterministic methods. The text reviews the mathematical analyses for modeling different biological systems such as the random processes continuous in time and discrete in state space. The book also discusses population growth and extinction through Malthus' law and the work of MacArthur and Wilson. The text then explains the dynamics of a population of interacting species. The book also addresses population genetics under systematic evolutionary pressures known as deterministic equations and genetic changes in a finite population known as stochastic equations. The text then turns to stochastic modeling of biological systems at the molecular level, particularly the kinetics of biochemical reactions. The book also presents various useful equations such as the differential equation for generating functions for birth and death processes. The text can prove valuable for biochemists, cellular biologists, and researchers in the medical and chemical field who are tasked to perform data analysis.
This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, this comprehensive book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources. Featuring numerous exercises and illustrations throughout, Biomolecular Feedback Systems is the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems. Provides a user-friendly introduction to essential concepts, tools, and applications Covers the most commonly used modeling methods Addresses the modular design problem for biomolecular systems Uses design examples from both natural systems and synthetic circuits Solutions manual (available only to professors at press.princeton.edu) An online illustration package is available to professors at press.princeton.edu
The aim of this book is to provide a well-structured and coherent overview of existing mathematical modeling approaches for biochemical reaction systems, investigating relations between both the conventional models and several types of deterministic-stochastic hybrid model recombinations. Another main objective is to illustrate and compare diverse numerical simulation schemes and their computational effort. Unlike related works, this book presents a broad scope in its applications, from offering a detailed introduction to hybrid approaches for the case of multiple population scales to discussing the setting of time-scale separation resulting from widely varying firing rates of reaction channels. Additionally, it also addresses modeling approaches for non well-mixed reaction-diffusion dynamics, including deterministic and stochastic PDEs and spatiotemporal master equations. Finally, by translating and incorporating complex theory to a level accessible to non-mathematicians, this book effectively bridges the gap between mathematical research in computational biology and its practical use in biological, biochemical, and biomedical systems.
This volume reviews the theory and simulation methods of stochastic kinetics by integrating historical and recent perspectives, presents applications, mostly in the context of systems biology and also in combustion theory. In recent years, due to the development in experimental techniques, such as optical imaging, single cell analysis, and fluorescence spectroscopy, biochemical kinetic data inside single living cells have increasingly been available. The emergence of systems biology brought renaissance in the application of stochastic kinetic methods.
