Computational modeling allows to reduce, refine and replace animal experimentation as well as to translate findings obtained in these experiments to the human background. However these biomedical problems are inherently complex with a myriad of influencing factors, which strongly complicates the model building and validation process. This book wants to address four main issues related to the building and validation of computational models of biomedical processes: 1. Modeling establishment under uncertainty 2. Model selection and parameter fitting 3. Sensitivity analysis and model adaptation 4. Model predictions under uncertainty In each of the abovementioned areas, the book discusses a number of key-techniques by means of a general theoretical description followed by one or more practical examples. This book is intended for graduate students and researchers active in the field of computational modeling of biomedical processes who seek to acquaint themselves with the different ways in which to study the parameter space of their model as well as its overall behavior.
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 volume covers a wide range of topics concerning methodological, epistemological, and regulatory-ethical issues around pharmacology. The book focuses in particular on the diverse sources of uncertainty, the different kinds of uncertainty that there are, and the diverse ways in which these uncertainties are (or could be) addressed. Compared with the more basic sciences, such as chemistry or biology, pharmacology works across diverse observable levels of reality: although the first step in the causal chain leading to the therapeutic outcome takes place at the biochemical level, the end-effect is a clinically observable result—which is influenced not only by biological actions, but also psychological and social phenomena. Issues of causality and evidence must be treated with these specific aspects in mind. In covering these issues, the book opens up a common domain of investigation which intersects the deeply intertwined dimensions of pharmacological research, pharmaceutical regulation and the related economic environment. The book is a collective endeavour with in-depth contributions from experts in pharmacology, philosophy of medicine, statistics, scientific methodology, formal and social epistemology, working in constant dialogue across disciplinary boundaries.
Anti-evolutionists, climate denialists, and anti-vaxxers, among others, question some of the best-established scientific findings by referring to the uncertainties in these areas of research. Uncertainty: How It Makes Science Advance shows that uncertainty is an inherent feature of science that makes it advance by motivating further research.
This book considers evolution at different scales: sequences, genes, gene families, organelles, genomes and species. The focus is on the mathematical and computational tools and concepts, which form an essential basis of evolutionary studies, indicate their limitations, and give them orientation. Recent years have witnessed rapid progress in the mathematics of evolution and phylogeny, with models and methods becoming more realistic, powerful, and complex. Aimed at graduates and researchers in phylogenetics, mathematicians, computer scientists and biologists, and including chapters by leading scientists: A. Bergeron, D. Bertrand, D. Bryant, R. Desper, O. Elemento, N. El-Mabrouk, N. Galtier, O. Gascuel, M. Hendy, S. Holmes, K. Huber, A. Meade, J. Mixtacki, B. Moret, E. Mossel, V. Moulton, M. Pagel, M.-A. Poursat, D. Sankoff, M. Steel, J. Stoye, J. Tang, L.-S. Wang, T. Warnow, Z. Yang, this book of contributed chapters explains the basis and covers the recent results in this highly topical area.
Ancestral sequence reconstruction is a technique of growing importance in molecular evolutionary biology and comparative genomics. As a powerful tool for testing evolutionary and ecological hypotheses, as well as uncovering the link between sequence and molecular phenotype, there are potential applications in a range of fields.Ancestral Sequence Reconstruction starts with a historical overview of the field, before discussing the potential applications in drug discovery and the pharmaceutical industry. This is followed by a section on computational methodology, which provides a detailed discussion of the available methods for reconstructing ancestral sequences (including their advantages, disadvantages, and potential pitfalls). Purely computational applications of the technique are then covered, including wholeproteome reconstruction. Further chapters provide a detailed discussion on taking computationally reconstructed sequences and synthesizing them in the laboratory. The book concludes with a description of the scientific questions where experimental ancestral sequence reconstruction has been utilized toprovide insights and inform future research.This research level text provides a first synthesis of the theories, methodologies and applications associated with ancestral sequence recognition, while simultaneously addressing many of the hot topics in the field. It will be of interest and use to both graduate students and researchers in the fields of molecular biology, molecular evolution, and evolutionary bioinformatics.
Modeling and Inverse Problems in the Presence of Uncertainty collects recent research-including the authors' own substantial projects-on uncertainty propagation and quantification. It covers two sources of uncertainty: where uncertainty is present primarily due to measurement errors and where uncertainty is present due to the modeling formulation i
Research on gene drive systems is rapidly advancing. Many proposed applications of gene drive research aim to solve environmental and public health challenges, including the reduction of poverty and the burden of vector-borne diseases, such as malaria and dengue, which disproportionately impact low and middle income countries. However, due to their intrinsic qualities of rapid spread and irreversibility, gene drive systems raise many questions with respect to their safety relative to public and environmental health. Because gene drive systems are designed to alter the environments we share in ways that will be hard to anticipate and impossible to completely roll back, questions about the ethics surrounding use of this research are complex and will require very careful exploration. Gene Drives on the Horizon outlines the state of knowledge relative to the science, ethics, public engagement, and risk assessment as they pertain to research directions of gene drive systems and governance of the research process. This report offers principles for responsible practices of gene drive research and related applications for use by investigators, their institutions, the research funders, and regulators.
In this provocative book, Paul Glimcher argues that economic theory may provide an alternative to the classical Cartesian model of the brain and behavior. Glimcher argues that Cartesian dualism operates from the false premise that the reflex is able to describe behavior in the real world that animals inhabit. A mathematically rich cognitive theory, he claims, could solve the most difficult problems that any environment could present, eliminating the need for dualism by eliminating the need for a reflex theory. Such a mathematically rigorous description of the neural processes that connect sensation and action, he explains, will have its roots in microeconomic theory. Economic theory allows physiologists to define both the optimal course of action that an animal might select and a mathematical route by which that optimal solution can be derived. Glimcher outlines what an economics-based cognitive model might look like and how one would begin to test it empirically. Along the way, he presents a fascinating history of neuroscience. He also discusses related questions about determinism, free will, and the stochastic nature of complex behavior.
