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.

A practice-oriented survey of techniques for computational modeling and simulation suitable for a broad range of biological problems. There are many excellent computational biology resources now available for learning about methods that have been developed to address specific biological systems, but comparatively little attention has been paid to training aspiring computational biologists to handle new and unanticipated problems. This text is intended to fill that gap by teaching students how to reason about developing formal mathematical models of biological systems that are amenable to computational analysis. It collects in one place a selection of broadly useful models, algorithms, and theoretical analysis tools normally found scattered among many other disciplines. It thereby gives the aspiring student a bag of tricks that will serve him or her well in modeling problems drawn from numerous subfields of biology. These techniques are taught from the perspective of what the practitioner needs to know to use them effectively, supplemented with references for further reading on more advanced use of each method covered. The text, which grew out of a class taught at Carnegie Mellon University, covers models for optimization, simulation and sampling, and parameter tuning. These topics provide a general framework for learning how to formulate mathematical models of biological systems, what techniques are available to work with these models, and how to fit the models to particular systems. Their application is illustrated by many examples drawn from a variety of biological disciplines and several extended case studies that show how the methods described have been applied to real problems in biology.

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

Aimed at postgraduate students in a variety of biology-related disciplines, this volume presents a collection of mathematical and computational single-cell-based models and their application. The main sections cover four general model groupings: hybrid cellular automata, cellular potts, lattice-free cells, and viscoelastic cells. Each section is introduced by a discussion of the applicability of the particular modelling approach and its advantages and disadvantages, which will make the book suitable for students starting research in mathematical biology as well as scientists modelling multicellular processes.

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.

Mathematical Models in Biology is an introductory book for readers interested in biological applications of mathematics and modeling in biology. A favorite in the mathematical biology community, it shows how relatively simple mathematics can be applied to a variety of models to draw interesting conclusions. Connections are made between diverse biological examples linked by common mathematical themes. A variety of discrete and continuous ordinary and partial differential equation models are explored. Although great advances have taken place in many of the topics covered, the simple lessons contained in this book are still important and informative. Audience: the book does not assume too much background knowledge--essentially some calculus and high-school algebra. It was originally written with third- and fourth-year undergraduate mathematical-biology majors in mind; however, it was picked up by beginning graduate students as well as researchers in math (and some in biology) who wanted to learn about this field.

The fast growing field of mathematical biology addresses biological questions using mathematical models from areas such as dynamical systems, probability, statistics, and discrete mathematics. This book considers models that are described by systems of partial differential equations, and it focuses on modeling, rather than on numerical methods and simulations. The models studied are concerned with population dynamics, cancer, risk of plaque growth associated with high cholesterol, and wound healing. A rich variety of open problems demonstrates the exciting challenges and opportunities for research at the interface of mathematics and biology. This book primarily addresses students and researchers in mathematics who do not necessarily have any background in biology and who may have had little exposure to PDEs.