Kinetic Modelling In Systems Biology

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 f

Although stochastic kinetic models are increasingly accepted as the best way to represent and simulate genetic and biochemical networks, most researchers in the field have limited knowledge of stochastic process theory. The stochastic processes formalism provides a beautiful, elegant, and coherent foundation for chemical kinetics and there is a wealth of associated theory every bit as powerful and elegant as that for conventional continuous deterministic models. The time is right for an introductory text written from this perspective. Stochastic Modelling for Systems Biology presents an accessible introduction to stochastic modelling using examples that are familiar to systems biology researchers. Focusing on computer simulation, the author examines the use of stochastic processes for modelling biological systems. He provides a comprehensive understanding of stochastic kinetic modelling of biological networks in the systems biology context. The text covers the latest simulation techniques and research material, such as parameter inference, and includes many examples and figures as well as software code in R for various applications. While emphasizing the necessary probabilistic and stochastic methods, the author takes a practical approach, rooting his theoretical development in discussions of the intended application. Written with self-study in mind, the book includes technical chapters that deal with the difficult problems of inference for stochastic kinetic models from experimental data. Providing enough background information to make the subject accessible to the non-specialist, the book integrates a fairly diverse literature into a single convenient and notationally consistent source.

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.

This detailed book provides an overview of various classes of computational techniques, including machine learning techniques, commonly used for evaluating kinetic parameters of biological systems. Focusing on three distinct situations, the volume covers the prediction of the kinetics of enzymatic reactions, the prediction of the kinetics of protein-protein or protein-ligand interactions (binding rates, dissociation rates, binding affinities), and the prediction of relatively large set of kinetic rates of reactions usually found in quantitative models of large biological networks. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of expert implementation advice that leads to successful results. Authoritative and practical, Computational Methods for Estimating the Kinetic Parameters of Biological Systems will be of great interest for researchers working through the challenge of identifying the best type of algorithm and who would like to use or develop a computational method for the estimation of kinetic parameters.

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.

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.

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 accessib.

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.

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 book delivers a comprehensive and insightful account of applying mathematical modelling approaches to very large biological systems and networks—a fundamental aspect of computational systems biology. The book covers key modelling paradigms in detail, while at the same time retaining a simplicity that will appeal to those from less quantitative fields. Key Features: A hands-on approach to modelling Covers a broad spectrum of modelling, from static networks to dynamic models and constraint-based models Thoughtful exercises to test and enable understanding of concepts State-of-the-art chapters on exciting new developments, like community modelling and biological circuit design Emphasis on coding and software tools for systems biology Companion website featuring lecture videos, figure slides, codes, supplementary exercises, further reading, and appendices: https://ramanlab.github.io/SysBioBook/ An Introduction to Computational Systems Biology: Systems-Level Modelling of Cellular Networks is highly multi-disciplinary and will appeal to biologists, engineers, computer scientists, mathematicians and others.