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

With the emergence of Systems Biology, there is a greater realization that the whole behavior of a living system may not be simply described as the sum of its elements. To represent a living system using mathematical principles, practical quantities with units are required. Quantities are not only the bridge between mathematical description and biological observations; they often stand as essential elements similar to genome information in genetics. This important realization has greatly rejuvenated research in the area of Quantitative Biology. Because of the increased need for precise quantification, a new era of technological development has opened. For example, spatio-temporal high-resolution imaging enables us to track single molecule behavior in vivo. Clever artificial control of experimental conditions and molecular structures has expanded the variety of quantities that can be directly measured. In addition, improved computational power and novel algorithms for analyzing theoretical models have made it possible to investigate complex biological phenomena. This research topic is organized on two aspects of technological advances which are the backbone of Quantitative Biology: (i) visualization of biomolecules, their dynamics and function, and (ii) generic technologies of model optimization and numeric integration. We have also included articles highlighting the need for new quantitative approaches to solve some of the long-standing cell biology questions. In the first section on visualizing biomolecules, four cutting-edge techniques are presented. Ichimura et al. provide a review of quantum dots including their basic characteristics and their applications (for example, single particle tracking). Horisawa discusses a quick and stable labeling technique using click chemistry with distinct advantages compared to fluorescent protein tags. The relatively small physical size, stability of covalent bond and simple metabolic labeling procedures in living cells provides this type of technology a potential to allow long-term imaging with least interference to protein function. Obien et al. review strategies to control microelectrodes for detecting neuronal activity and discuss techniques for higher resolution and quality of recordings using monolithic integration with on-chip circuitry. Finally, the original research article by Amariei et al. describes the oscillatory behavior of metabolites in bacteria. They describe a new method to visualize the periodic dynamics of metabolites in large scale cultures populations. These four articles contribute to the development of quantitative methods visualizing diverse targets: proteins, electrical signals and metabolites. In the second section of the topic, we have included articles on the development of computational tools to fully harness the potential of quantitative measurements through either calculation based on specific model or validation of the model itself. Kimura et al. introduce optimization procedures to search for parameters in a quantitative model that can reproduce experimental data. They present four examples: transcriptional regulation, bacterial chemotaxis, morphogenesis of tissues and organs, and cell cycle regulation. The original research article by Sumiyoshi et al. presents a general methodology to accelerate stochastic simulation efforts. They introduce a method to achieve 130 times faster computation of stochastic models by applying GPGPU. The strength of such accelerated numerical calculation are sometimes underestimated in biology; faster simulation enables multiple runs and in turn improved accuracy of numerical calculation which may change the final conclusion of modeling study. This also highlights the need to carefully assess simulation results and estimations using computational tools.

Quantitative methods are revolutionizing modern molecular and cellular biology. Groundbreaking technical advances are fueling the rapid expansion in our ability to observe, as seen in multidisciplinary studies that integrate theory, computation, experimental assays, and the control of microenvironments. Integrating new experimental and theoretical methods, Quantitative Biology: From Molecular to Cellular Systems gives both new and established researchers a solid foundation for starting work in this field. The book is organized into three sections: Fundamental Concepts covers bold ideas that inspire novel approaches in modern quantitative biology. It offers perspectives on evolutionary dynamics, system design principles, chance and memory, and information processing in biology. Methods describes recently developed or improved techniques that are transforming biological research. It covers experimental methods for studying single-molecule biochemistry, small-angle scattering from biomolecules, subcellular localization of proteins, and single-cell behavior. It also describes theoretical methods for synthetic biology and modeling random variations among cells. Molecular and Cellular Systems focuses on specific biological systems where modern quantitative biology methods are making an impact. It incorporates case studies of biological systems for which new concepts or methods are increasing our understanding. Examples include protein kinase at the molecular level, the genetic switch of phage lambda at the regulatory system level, and Escherichia coli chemotaxis at the cellular level. In short, Quantitative Biology presents practical tools for the observation, modeling, design, and manipulation of biological systems from the molecular to the cellular levels.

From the spontaneous rapid firing of cortical neurons to the spatial diffusion of disease epidemics, biological systems exhibit rich dynamic behaviour over a vast range of time and space scales. Unifying many of these diverse phenomena, Dynamics of Biological Systems provides the computational and mathematical platform from which to understand the underlying processes of the phenomena. Through an extensive tour of various biological systems, the text introduces computational methods for simulating spatial diffusion processes in excitable media, such as the human heart, as well as mathematical tools for dealing with systems of nonlinear ordinary and partial differential equations, such as neuronal activation and disease diffusion. The mathematical models and computer simulations offer insight into the dynamics of temporal and spatial biological systems, including cardiac pacemakers, artificial electrical defibrillation, pandemics, pattern formation, flocking behaviour, the interaction of autonomous agents, and hierarchical and structured network topologies. Tools from complex systems and complex networks are also presented for dealing with real phenomenological systems. With exercises and projects in each chapter, this classroom-tested text shows students how to apply a variety of mathematical and computational techniques to model and analyze the temporal and spatial phenomena of biological systems. MATLAB® implementations of algorithms and case studies are available on the author’s website.

Thorough and accessible, this book presents the design principles of biological systems, and highlights the recurring circuit elements that make up biological networks. It provides a simple mathematical framework which can be used to understand and even design biological circuits. The textavoids specialist terms, focusing instead on several well-studied biological systems that concisely demonstrate key principles. An Introduction to Systems Biology: Design Principles of Biological Circuits builds a solid foundation for the intuitive understanding of general principles. It encourages the reader to ask why a system is designed in a particular way and then proceeds to answer with simplified models.

An overview of current models of biological systems, reflecting the major advances that have been made over the past decade.

Written for intermediate-level undergraduates pursuing any science or engineering major, Physical Models of Living Systems helps students develop many of the competencies that form the basis of the new MCAT2015. The only prerequisite is first-year physics. With the more advanced "Track-2" sections at the end of each chapter, the book can be used in graduate-level courses as well.