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Markov Chain Monte Carlo (MCMC) methods are sampling based techniques, which use random numbers to approximate deterministic but unknown values. They can be used to obtain expected values, estimate parameters or to simply inspect the properties of a non-standard, high dimensional probability distribution. Bayesian analysis of model parameters provides the mathematical foundation for parameter estimation using such probabilistic sampling. The strengths of these stochastic methods are their robustness and relative simplicity even for nonlinear problems with dozens of parameters as well as a built-in uncertainty analysis. Because Bayesian model analysis necessarily involves the notion of prior knowledge, the estimation of unidentifiable parameters can be regularised (by priors) in a straight forward way. This work draws the focus on typical cases in systems biology: relative data, nonlinear ordinary differential equation models and few data points. It also investigates the consequences of parameter estimation from steady state data; consequences such as performance benefits. In biology the data is almost exclusively relative, the raw measurements (e.g. western blot intensities) are normalised by control experiments or a reference value within a series and require the model to do the same when comparing its output to the data. Several sampling algorithms are compared in terms of effective sampling speed and necessary adaptations to relative and steady state data are explained.
System Biology encompasses the knowledge from diverse fields such as Molecular Biology, Immunology, Genetics, Computational Biology, Mathematical Biology, etc. not only to address key questions that are not answerable by individual fields alone, but also to help in our understanding of the complexities of biological systems. Whole genome expression studies have provided us the means of studying the expression of thousands of genes under a particular condition and this technique had been widely used to find out the role of key macromolecules that are involved in biological signaling pathways. However, making sense of the underlying complexity is only possible if we interconnect various signaling pathways into human and computer readable network maps. These maps can then be used to classify and study individual components involved in a particular phenomenon. Apart from transcriptomics, several individual gene studies have resulted in adding to our knowledge of key components that are involved in a signaling pathway. It therefore becomes imperative to take into account of these studies also, while constructing our network maps to highlight the interconnectedness of the entire signaling pathways and the role of that particular individual protein in the pathway. This collection of articles will contain a collection of pioneering work done by scientists working in regulatory signaling networks and the use of large scale gene expression and omics data. The distinctive features of this book would be: Act a single source of information to understand the various components of different signaling network (roadmap of biochemical pathways, the nature of a molecule of interest in a particular pathway, etc.), Serve as a platform to highlight the key findings in this highly volatile and evolving field, and Provide answers to various techniques both related to microarray and cell signaling to the readers.
Systems biology is a critical emerging field that quantifies and annotates the complexity of biological systems in order to construct algorithmic models to predict outcomes from component input. Applications in medicine are revolutionizing our understanding of biological processes and systems. Systems Biomedicine is organized around foundations, computational modeling, network biology, and integrative biology, with the extension of examples from human biology and pharmacology, to focus on the applications of systems approaches to medical problems. An integrative approach to the underlying genomic, proteomic, and computational biology principles provides researchers with guidance in the use of qualitative systems and hypothesis generators. To reflect the highly interdisciplinary nature of the field, careful detail has been extended to ensure explanations of complex mathematical and biological principles are clear with minimum technical jargon. - Organized to reflect the important distinguishing characteristics of systems strategies in experimental biology and medicine - Provides precise and comprehensive measurement tools for constructing a model of the system and tools for defining complexity as an experimental dependent variable - Includes a thorough discussion of the applications of quantitative principles to biomedical problems
This book constitutes the refereed proceedings of the 13th International Conference on Computational Methods in Systems Biology, CMSB 2015, held in Nantes, France, in September 2015. The 20 full papers and 2 short papers presented were carefully reviewed and selected from 43 full and 4 short paper submissions. The papers cover a wide range of topics in the analysis of biological systems, networks and data such as model checking, stochastic analysis, hybrid systems, circadian clock, time series data, logic programming, and constraints solving ranging from intercellular to multiscale.
Current Biomedical Databases are independently administered in geographically distinct locations, lending them almost ideally to adoption of intelligent data management approaches. This book focuses on research issues, problems and opportunities in Biomedical Data Infrastructure identifying new issues and directions for future research in Biomedical Data and Information Retrieval, Semantics in Biomedicine, and Biomedical Data Modeling and Analysis. The book will be a useful guide for researchers, practitioners, and graduate-level students interested in learning state-of-the-art development in biomedical data management.
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.
Stochastic kinetic methods are currently considered to be the most realistic and elegant means of representing and simulating the dynamics of biochemical and biological networks. Deterministic versus stochastic modelling in biochemistry and systems biology introduces and critically reviews the deterministic and stochastic foundations of biochemical kinetics, covering applied stochastic process theory for application in the field of modelling and simulation of biological processes at the molecular scale. Following an overview of deterministic chemical kinetics and the stochastic approach to biochemical kinetics, the book goes onto discuss the specifics of stochastic simulation algorithms, modelling in systems biology and the structure of biochemical models. Later chapters cover reaction-diffusion systems, and provide an analysis of the Kinfer and BlenX software systems. The final chapter looks at simulation of ecodynamics and food web dynamics. Introduces mathematical concepts and formalisms of deterministic and stochastic modelling through clear and simple examples Presents recently developed discrete stochastic formalisms for modelling biological systems and processes Describes and applies stochastic simulation algorithms to implement a stochastic formulation of biochemical and biological kinetics
This book constitutes the thoroughly refereed post-workshop proceedings of the Second International Workshop on Hybrid Systems Biology, HSB 2013, held as part of the ECAL 2013 event, in Taormina, Italy, in September 2013; and the Third International Workshop on Hybrid Systems Biology, HSB 2014, held as part of CAV 2014, in Vienna, Austria, in July 2014. This volume presents 8 full papers together with 2 invited tutorials/surveys from 21 submissions. The HSB 2013 workshop aims at collecting scientists working in the area of hybrid modeling applied to systems biology, in order to discuss about current achieved goals, current challenges and future possible developments. The scope of the HSB 2014 workshop is the general area of dynamical models in biology with an emphasis on hybrid approaches, which are not restricted to a narrow class of mathematical models, and which take advantage of techniques developed separately in different sub-fields. “br> /div
Dynamic Systems Biology Modeling and Simuation consolidates and unifies classical and contemporary multiscale methodologies for mathematical modeling and computer simulation of dynamic biological systems – from molecular/cellular, organ-system, on up to population levels. The book pedagogy is developed as a well-annotated, systematic tutorial – with clearly spelled-out and unified nomenclature – derived from the author's own modeling efforts, publications and teaching over half a century. Ambiguities in some concepts and tools are clarified and others are rendered more accessible and practical. The latter include novel qualitative theory and methodologies for recognizing dynamical signatures in data using structural (multicompartmental and network) models and graph theory; and analyzing structural and measurement (data) models for quantification feasibility. The level is basic-to-intermediate, with much emphasis on biomodeling from real biodata, for use in real applications. - Introductory coverage of core mathematical concepts such as linear and nonlinear differential and difference equations, Laplace transforms, linear algebra, probability, statistics and stochastics topics - The pertinent biology, biochemistry, biophysics or pharmacology for modeling are provided, to support understanding the amalgam of "math modeling with life sciences - Strong emphasis on quantifying as well as building and analyzing biomodels: includes methodology and computational tools for parameter identifiability and sensitivity analysis; parameter estimation from real data; model distinguishability and simplification; and practical bioexperiment design and optimization - Companion website provides solutions and program code for examples and exercises using Matlab, Simulink, VisSim, SimBiology, SAAMII, AMIGO, Copasi and SBML-coded models - A full set of PowerPoint slides are available from the author for teaching from his textbook. He uses them to teach a 10 week quarter upper division course at UCLA, which meets twice a week, so there are 20 lectures. They can easily be augmented or stretched for a 15 week semester course - Importantly, the slides are editable, so they can be readily adapted to a lecturer's personal style and course content needs. The lectures are based on excerpts from 12 of the first 13 chapters of DSBMS. They are designed to highlight the key course material, as a study guide and structure for students following the full text content - The complete PowerPoint slide package (~25 MB) can be obtained by instructors (or prospective instructors) by emailing the author directly, at: [email protected]