Design And Analysis Of Biomolecular Circuits

The book deals with engineering aspects of the two emerging and intertwined fields of synthetic and systems biology. Both fields hold promise to revolutionize the way molecular biology research is done, the way today’s drug discovery works and the way bio-engineering is done. Both fields stress the importance of building and characterizing small bio-molecular networks in order to synthesize incrementally and understand large complex networks inside living cells. Reminiscent of computer-aided design (CAD) of electronic circuits, abstraction is believed to be the key concept to achieve this goal. It allows hiding the overwhelming complexity of cellular processes by encapsulating network parts into abstract modules. This book provides a unique perspective on how concepts and methods from CAD of electronic circuits can be leveraged to overcome complexity barrier perceived in synthetic and systems biology.

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

This textbook introduces readers to the recent advances in the emerging field of genetic design automation (GDA). Starting with an introduction and the basic concepts of molecular biology, the authors provide an overview of various genetic design automation tools. The authors then present the DVASim tool (Dynamic Virtual Analyzer and Simulator) which is used for the analysis and verification of genetic logic circuits. This includes methods and algorithms for the timing and threshold value analyses of genetic logic circuits. Next, the book presents the GeneTech tool (A technology mapping tool for genetic circuits) and the methods developed for optimization, synthesis, and technology mapping of genetic circuits. Chapters are followed by exercises which give readers hands-on practice with the tools presented. The concepts and algorithms are thoroughly described, enabling readers to improve the tools or use them as a starting point to develop new tools. Both DVASim and GeneTech are available from the developer’s website, free of charge. This book is intended for a multidisciplinary audience of computer scientists, engineers and biologists. It provides enough background knowledge for computer scientists and engineers, who usually do not have any background in biology but are interested to get involved in this domain. This book not only presents an accessible basic introduction to molecular biology, it also includes software tools which allow users to perform laboratory experiments in a virtual in-silico environment. This helps newbies to get a quick start in understanding and developing genetic design automation tools. The third part of this book is particular useful for biologists who usually find it difficult to grasp programming and are reluctant to developing computer software. They are introduced to the graphical programming language, LabVIEW, from which they can start developing computer programs rapidly. Readers are further provided with small projects which will help them to start developing GDA tools.

This Festschrift is published in honor of Kim Guldstrand Larsen, one of the earliest precursors of computer science in Denmark, on the occasion of his 60th birthday. During the last three decades, Kim Guldstrand Larsen has given major contributions across a remarkably wide range of topics, including real-time, concurrent, and probabilistic models of computation, logic in computer science, and model checking. Since 1995, he has been one of the prime movers behind the model checking tool for real-time systems UPPAAL, for which he was a co-recipient of the CAV Award in 2013. The Festschrift contains 32 papers that feature the broad range of Kim Guldstrand Larsen's research topics, such as formal languages and automata theory; logic; verification, model checking and testing; algorithmic game theory and mechanism design; semantics and reasoning; real-time and distributed systems; and modeling and simulation.

Algebraic and Combinatorial Computational Biology introduces students and researchers to a panorama of powerful and current methods for mathematical problem-solving in modern computational biology. Presented in a modular format, each topic introduces the biological foundations of the field, covers specialized mathematical theory, and concludes by highlighting connections with ongoing research, particularly open questions. The work addresses problems from gene regulation, neuroscience, phylogenetics, molecular networks, assembly and folding of biomolecular structures, and the use of clustering methods in biology. A number of these chapters are surveys of new topics that have not been previously compiled into one unified source. These topics were selected because they highlight the use of technique from algebra and combinatorics that are becoming mainstream in the life sciences. Integrates a comprehensive selection of tools from computational biology into educational or research programs Emphasizes practical problem-solving through multiple exercises, projects and spinoff computational simulations Contains scalable material for use in undergraduate and graduate-level classes and research projects Introduces the reader to freely-available professional software Supported by illustrative datasets and adaptable computer code

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

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.