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.

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.

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 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 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.

Systems Biology is now entering a mature phase in which the key issues are characterising uncertainty and stochastic effects in mathematical models of biological systems. The area is moving towards a full statistical analysis and probabilistic reasoning over the inferences that can be made from mathematical models. This handbook presents a comprehensive guide to the discipline for practitioners and educators, in providing a full and detailed treatment of these important and emerging subjects. Leading experts in systems biology and statistics have come together to provide insight in to the major ideas in the field, and in particular methods of specifying and fitting models, and estimating the unknown parameters. This book: Provides a comprehensive account of inference techniques in systems biology. Introduces classical and Bayesian statistical methods for complex systems. Explores networks and graphical modeling as well as a wide range of statistical models for dynamical systems. Discusses various applications for statistical systems biology, such as gene regulation and signal transduction. Features statistical data analysis on numerous technologies, including metabolic and transcriptomic technologies. Presents an in-depth presentation of reverse engineering approaches. Provides colour illustrations to explain key concepts. This handbook will be a key resource for researchers practising systems biology, and those requiring a comprehensive overview of this important field.

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.

Tools and techniques for biological inference problems at scales ranging from genome-wide to pathway-specific. Computational systems biology unifies the mechanistic approach of systems biology with the data-driven approach of computational biology. Computational systems biology aims to develop algorithms that uncover the structure and parameterization of the underlying mechanistic model--in other words, to answer specific questions about the underlying mechanisms of a biological system--in a process that can be thought of as learning or inference. This volume offers state-of-the-art perspectives from computational biology, statistics, modeling, and machine learning on new methodologies for learning and inference in biological networks.The chapters offer practical approaches to biological inference problems ranging from genome-wide inference of genetic regulation to pathway-specific studies. Both deterministic models (based on ordinary differential equations) and stochastic models (which anticipate the increasing availability of data from small populations of cells) are considered. Several chapters emphasize Bayesian inference, so the editors have included an introduction to the philosophy of the Bayesian approach and an overview of current work on Bayesian inference. Taken together, the methods discussed by the experts in Learning and Inference in Computational Systems Biology provide a foundation upon which the next decade of research in systems biology can be built. Florence d'Alch e-Buc, John Angus, Matthew J. Beal, Nicholas Brunel, Ben Calderhead, Pei Gao, Mark Girolami, Andrew Golightly, Dirk Husmeier, Johannes Jaeger, Neil D. Lawrence, Juan Li, Kuang Lin, Pedro Mendes, Nicholas A. M. Monk, Eric Mjolsness, Manfred Opper, Claudia Rangel, Magnus Rattray, Andreas Ruttor, Guido Sanguinetti, Michalis Titsias, Vladislav Vyshemirsky, David L. Wild, Darren Wilkinson, Guy Yosiphon

An introduction to the quantitative modeling of biological processes, presenting modeling approaches, methodology, practical algorithms, software tools, and examples of current research. The quantitative modeling of biological processes promises to expand biological research from a science of observation and discovery to one of rigorous prediction and quantitative analysis. The rapidly growing field of quantitative biology seeks to use biology's emerging technological and computational capabilities to model biological processes. This textbook offers an introduction to the theory, methods, and tools of quantitative biology. The book first introduces the foundations of biological modeling, focusing on some of the most widely used formalisms. It then presents essential methodology for model-guided analyses of biological data, covering such methods as network reconstruction, uncertainty quantification, and experimental design; practical algorithms and software packages for modeling biological systems; and specific examples of current quantitative biology research and related specialized methods. Most chapters offer problems, progressing from simple to complex, that test the reader's mastery of such key techniques as deterministic and stochastic simulations and data analysis. Many chapters include snippets of code that can be used to recreate analyses and generate figures related to the text. Examples are presented in the three popular computing languages: Matlab, R, and Python. A variety of online resources supplement the the text. The editors are long-time organizers of the Annual q-bio Summer School, which was founded in 2007. Through the school, the editors have helped to train more than 400 visiting students in Los Alamos, NM, Santa Fe, NM, San Diego, CA, Albuquerque, NM, and Fort Collins, CO. This book is inspired by the school's curricula, and most of the contributors have participated in the school as students, lecturers, or both. Contributors John H. Abel, Roberto Bertolusso, Daniela Besozzi, Michael L. Blinov, Clive G. Bowsher, Fiona A. Chandra, Paolo Cazzaniga, Bryan C. Daniels, Bernie J. Daigle, Jr., Maciej Dobrzynski, Jonathan P. Doye, Brian Drawert, Sean Fancer, Gareth W. Fearnley, Dirk Fey, Zachary Fox, Ramon Grima, Andreas Hellander, Stefan Hellander, David Hofmann, Damian Hernandez, William S. Hlavacek, Jianjun Huang, Tomasz Jetka, Dongya Jia, Mohit Kumar Jolly, Boris N. Kholodenko, Markek Kimmel, Michał Komorowski, Ganhui Lan, Heeseob Lee, Herbert Levine, Leslie M Loew, Jason G. Lomnitz, Ard A. Louis, Grant Lythe, Carmen Molina-París, Ion I. Moraru, Andrew Mugler, Brian Munsky, Joe Natale, Ilya Nemenman, Karol Nienałtowski, Marco S. Nobile, Maria Nowicka, Sarah Olson, Alan S. Perelson, Linda R. Petzold, Sreenivasan Ponnambalam, Arya Pourzanjani, Ruy M. Ribeiro, William Raymond, William Raymond, Herbert M. Sauro, Michael A. Savageau, Abhyudai Singh, James C. Schaff, Boris M. Slepchenko, Thomas R. Sokolowski, Petr Šulc, Andrea Tangherloni, Pieter Rein ten Wolde, Philipp Thomas, Karen Tkach Tuzman, Lev S. Tsimring, Dan Vasilescu, Margaritis Voliotis, Lisa Weber