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The vast amount of knowledge in Cell Signaling gathered through reductionist efforts and omics technology is poised to approach a Systems Biology understanding of precise representations of cell structure and function and predictions at multi-scale levels despite the complexity. Super-resolution microscopy and single cell analysis are also providing opportunities to explore both spatial and temporal landscapes. Notably, many basic biological processes have been studied capturing mechanistic detail with the goal to understand cellular proliferation and differentiation, gene regulation, morphogenesis, metabolism, and cell-cell communication. Similarly, at the intracellular level, addressing functions such as self-assembly, phase separation, and transport is leading to insights not readily understood as linear pathways. Therefore, network-based mathematical modeling, delineating dynamic biochemical reactions through ordinary and partial differential equations, promises to discover emergent biological properties not heretofore expected.
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.
Key introductory text for graduate students and researchers in physics, biology and biochemistry.
Computational Immunology: Models and Tools encompasses the methodological framework and application of cutting-edge tools and techniques to study immunological processes at a systems level, along with the concept of multi-scale modeling. The book's emphasis is on selected cases studies and application of the most updated technologies in computational modeling, discussing topics such as computational modeling and its usage in immunological research, bioinformatics infrastructure, ODE based modeling, agent based modeling, and high performance computing, data analytics, and multiscale modeling. There are also modeling exercises using recent tools and models which lead the readers to a thorough comprehension and applicability. The book is a valuable resource for immunologists, computational biologists, bioinformaticians, biotechnologists, and computer scientists, as well as all those who wish to broaden their knowledge in systems modeling. - Offers case studies with different levels of complexity - Provides a detailed view on cutting-edge tools for modeling that are useful to experimentalists with limited computational skills - Explores the usage of simulation for hypothesis generation, helping the reader to understand the most valuable points on experimental setting
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.
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.
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.
Mathematical models have become invaluable tools for understanding the intricate dynamic behavior of complex biochemical and biological systems. Among computational strategies, logical modeling has been recently gaining interest as an alternative approach to address network dynamics. Due to its advantages, including scalability and independence of kinetic parameters, the logical modeling framework is becoming increasingly popular to study the dynamics of highly interconnected systems, such as cell cycle progression, T cell differentiation and gene regulation. Novel tools and standards have been developed to increase the interoperability of logical models, which can now be employ to respond a variety of biological questions. This Research Topic brings together the most recent and cutting-edge approaches in the area of logical modeling including, among others, novel biological applications, software development and model analysis techniques.
Mathematical modelling in biomedicine is a rapidly developing scientific discipline at the intersection of medicine, biology, mathematics, physics, and computer science. Its progress is stimulated by fundamental scientific questions and by the applications to public health. This book represents a collection of papers devoted to mathematical modelling of various physiological problems in normal and pathological conditions. It covers a broad range of topics including cardiovascular system and diseases, heart and brain modelling, tumor growth, viral infections, and immune response. Computational models of blood circulation are used to study the influence of heart arrhythmias on coronary blood flow and on operating modes for left-ventricle-assisted devices. Wave propagation in the cardiac tissue is investigated in order to show the influence of tissue heterogeneity and fibrosis. The models of tumor growth are used to determine optimal protocols of antiangiogenic and radiotherapy. The models of viral hepatitis kinetics are considered for the parameter identification, and the evolution of viral quasi-species is investigated. The book presents the state-of-the-art in mathematical modelling in biomedicine and opens new perspectives in this passionate field of research.
This open access volume presents a novel computational framework for understanding how collections of excitable cells work. The key approach in the text is to model excitable tissue by representing the individual cells constituting the tissue. This is in stark contrast to the common approach where homogenization is used to develop models where the cells are not explicitly present. The approach allows for very detailed analysis of small collections of excitable cells, but computational challenges limit the applicability in the presence of large collections of cells.