Download or read book Macroscopic Modeling of Metabolic Reaction Networks and Dynamic Identification of Elementary Flux Modes by Column Generation written by and published by . This book was released on 2015 with total page 146 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Metabolic Networks Elementary Flux Modes and Polyhedral Cones written by Isaac Klapper and published by SIAM. This book was released on 2021-06-15 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents a mathematical analysis of the relationship between the cell biology idea of metabolic networks and the mathematical idea of polyhedral cones. Such cones can be used to describe the set of steady state admissible fluxes through metabolic networks, and consequently they have become important constructs in the field of microbiology. Fundamental objects called elementary flux modes (EFMs) can be described mathematically via convex cone concepts; the fundamental algorithm of this relationship is the Double Description method. While this method has an extended history in the field of computational geometry, this monograph addresses its relatively recent use in the context of cellular metabolism, providing an easy-to-read introduction to a central topic of mathematical systems biology. Metabolic Networks, Elementary Flux Modes, and Polyhedral Cones addresses important topics in the mathematical description of metabolic activity that have not previously appeared in unified form and presents a careful study of the Double Description method in the context of metabolic analysis. It makes mathematical aspects of the material readily accessible to bioengineers and system biologists, and biological aspects readily accessible to mathematicians. This book is intended for readers from both mathematical and biological backgrounds, including mathematicians, engineers, and biologists interested in cell metabolism. It will also be helpful to mathematicians interested in applying computational geometry methods in computational biology as well as for systems biologists and modelers interested in the mathematical and algorithmic foundations of metabolic pathway analysis.

Download or read book Metabolic Network Reconstruction and Modeling written by Marco Fondi and published by Humana Press. This book was released on 2018-08-30 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume looks at the latest methodologies used to study cellular metabolism with in silico approaches. The chapters in this book are divided into 3 parts: part I discusses tools and methods used for metabolic reconstructions and basic constraint-based metabolic modeling (CBMM); Part II explores protocols for the generation of experimental data for metabolic reconstruction and modeling, including transcriptomics, proteomics, and mutant generations; and Part III cover advanced techniques for quantitative modeling of cellular metabolism, including dynamic Flux Balance Analysis and multi-objective optimization. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Metabolic Network Reconstruction and Modeling: Methods and Protocols is a valuable resource for qualified investigators studying cellular metabolism, and novice researchers who want to start working with CBMM.

Download or read book The Mathematical Modeling of Metabolic and Endocrine Systems written by Ewart R. Carson and published by . This book was released on 1983-02-25 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: Introduces the concepts, methods and techniques of model formulation, identification, and validation as applicable to metabolic and endocrine processes. Shows how modeling can be used to provide a concise description of complex dynamic processes, to test hypotheses concerning physiological and biochemical structure, and to estimate physiological quantities (parameters) that otherwise would not be directly accessible to measurement. Includes numerous examples and case studies.

Download or read book A Decomposition Approach for Computing Elementary Flux Modes in Genome scale Metabolic Networks written by Siu-hung Joshua Chan and published by . This book was released on 2011 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dynamic Models of Metabolic Networks and Analysis of Cell free Protein Synthesis written by Michael Vilkhovoy and published by . This book was released on 2019 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolism is the central process through which cells manage their resources to survive, adapt and meet energetic demands. To implement these diverse functions, cells have complex and highly interconnected networks of chemical reactions between genes, RNA, proteins and metabolites. Systems modeling and metabolic engineering arose from the desire to harness the power of metabolism to produce products that benefit society. A primary challenge is the development of metabolic mathematical models that are able to describe the effect genetic perturbations have on cellular behavior. In this study, we first review metabolic modeling methods and go on to develop computational tools for the analysis and engineering of microbial systems with a focus on cell-free protein synthesis (CFPS). Cell-free protein expression has become a widely used research tool in systems and synthetic biology, and a promising technology for biomanufacturing of proteins. Cell-free systems offer many advantages for the study, manipulation and modeling of metabolism compared to in vivo processes. Central amongst these is direct access to metabolites and the biosynthetic machinery without the interference of a cell wall or the complications associated with cell growth. However, if CFPS is to become a mainstream technology for applications such as point of care manufacturing, we must understand the performance limits and costs of these systems. Cell-free protein synthesis relies on transcription and translation machinery to produce a protein of interest. To fuel this process requires biochemical enzymes and reactions that are involved in complex metabolic pathways. Toward this, we developed dynamic mathematical models that describe CFPS metabolism and provide insights into improving these systems. We began with a sequence specific constraint based model that coupled transcription/translation processes and the regulation of gene expression with the availability of metabolic resources. Then, we developed a robust comprehensive analysis to quantify absolute levels of metabolites in CFPS using isotopically labeled standards. We expanded our modeling framework by integrating absolute metabolite measurements along with kinetic parameters, enzyme levels, and enzyme activity assays. The framework predicted the overall production of mRNA and protein along with changes in metabolic behavior with two different oxidative phosphorylation inhibitors. Taken together, we provided a comprehensive mathematical framework of CFPS metabolism that could be used to identify strategies for the improvement of CFPS productivity, yield and efficiency.

Download or read book Analysis of Large Scale Metabolic Networks written by Christoph Kaleta and published by . This book was released on 2010 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Plant Metabolic Flux Analysis written by Martine Dieuaide-Noubhani and published by Humana Press. This book was released on 2013-11-13 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Plant Metabolic Flux Analysis, expert researchers in the field provide detailed experimental procedures for each step of the flux quantification workflow. Steady state and dynamic modeling are considered, as well as recent developments for the reconstruction of metabolic networks and for a predictive modeling. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical Plant Metabolic Flux Analysis, seeks to aid scientists in the further study of cutting-edge protocols and methodologies that are crucial to getting ahead in MFA.

Download or read book On the Systems Characterization of Metabolic Networks written by Neema Jamshidi and published by . This book was released on 2009 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt: Significant progress has been made in the development of genome-scale models of metabolism in the past 15 years. The majority of the efforts have focused on the analysis of the right null space. While the steady state solution space is very important since homeostatic mechanisms are continuously trying to push the system back to a steady state, there are three other subspaces which also have significance. This dissertation approaches metabolic networks with the goal of investigating all four fundamental subspaces of linear systems, particularly the row and column spaces, which determine the dynamic capabilities of networks. First, the key matrices are defined and their general properties and characteristics are identified. The subspaces are analyzed for a simple metabolic network. Next the right null space is explored in a targeted manner using real networks, the cardiomyocyte mitochondria and a genome-scale model of Mycobacterium tuberculosis, focusing on perfectly correlated reaction sets and the biologically interesting implications they may hold. This is followed by the development of analytical methods to define the time scale hierarchy in the column space of the human red cell, human folate metabolism, and yeast glycolysis. These studies are further pursued by investigating various decompositions of the stoichiometric and gradient matrices that are determined by the underlying physico-chemical characteristics. These investigations lead to the identification of key properties of metabolic networks, such as the duality between fluxes and concentrations in dynamic networks. Having established how to decompose these networks, a middle-out integration approach is described for building or reconstructing kinetic networks using '-omic' data streams that are increasingly available. This approach is applied to construct a dynamic model of human red cell metabolism with and without mechanistic integration of allosteric regulatory functions of enzymes, dynamic models of E. coli, as well as a general hepatocyte mitochondria model which can be used for application of these methods, when the appropriate data becomes available. Simulations with the regulated erythrocyte model highlight the importance of active versus inactive states of enzymes and how the binding state of the enzyme exerts control of the flux through competing pathways. The subsequent chapter investigates perturbational analyses and how they can inform functional states and identify pathophysiological conditions. This dissertation culminates in a description of a conceptually new approach to modeling, 'delta' networks, that relaxes data requirements and is focused on identifying the functional differences between different data sets in an effort to understand as much of the four subspaces as possible, not just the right null space. The studies carried out in this dissertation also further support the use of models as data interrogation tools; for data integration, analysis, as well as for the evaluation of data consistency. The developments and advancements made herein take steps towards achieving genome-scale dynamic regulated networks of metabolism, which can in principle be applied to any biological network.

Download or read book Identification of Dynamic Metabolic Flux Balance Models Based on Parametric Sensitivity Analysis written by Ricardo Martinez Villegas and published by . This book was released on 2016 with total page 103 pages. Available in PDF, EPUB and Kindle. Book excerpt: A dynamic mathematical model that involves a set of physicochemical parameters can describe a dynamic system. Parametric sensitivity analysis studies the effect of changes in these parameters on model outputs of interest. If a system is operated within a region of high sensitivity any small change in the parameter values drastically affect the output. Hence, it is essential to be able to predict this sensitivity when designing, operating or optimizing a system based on the model. Dynamical biological models that describe gene regulation, signalling, and metabolic networks are strongly dependent on a large number of parameters. Most of these models are highly nonlinear and involve a high-dimensional state space. Conventional parametric sensitivity analysis that examines the effect of each parameter independently at one specific moment is generally inaccurate since it ignores correlations between parameters. Thus, it is very important to account for correlations when conducting a parametric sensitivity analysis.

Download or read book Models and Algorithms for Metabolic Networks written by Vicente Acuna and published by . This book was released on 2010 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this PhD, we present some algorithms and complexity results for two general problems that arise in the analysis of a metabolic network: the search for elementary modes of a network and the search for minimal precursors sets. Elementary modes is a common tool in the study of the cellular characteristic of a metabolic network. An elementary mode can be seen as a minimal set of reactions that can work in steady state independently of the rest of the network. It has therefore served as a mathematical model for the possible metabolic pathways of a cell. Their computation is not trivial and poses computational challenges. We show that some problems, like checking consistency of a network, finding one elementary mode or checking that a set of reactions constitutes a cut are easy problems, giving polynomial algorithms based on LP formulations. We also prove the hardness of central problems like finding a minimum size elementary mode, finding an elementary mode containing two given reactions, counting the number of elementary modes or finding a minimum reaction cut. On the enumeration problem, we show that enumerating all reactions containing one given reaction cannot be done in polynomial total time unless P=NP. This result provides some idea about the complexity of enumerating all the elementary modes. The search for precursor sets is motivated by discovering which external metabolites are sufficient to allow the production of a given set of target metabolites. In contrast with previous proposals, we present a new approach which is the first to formally consider the use of cycles in the way to produce the target. We present a polynomial algorithm to decide whether a set is a precursor set of a given target. We also show that, given a target set, finding a minimal precursor set is easy but finding a precursor set of minimum size is NP-hard. We further show that finding a solution with minimum size internal supply is NP-hard. We give a simple characterisation of precursors sets by the existence of hyperpaths between the solutions and the target. If we consider the enumeration of all the minimal precursor sets of a given target, we find that this problem cannot be solved in polynomial total time unless P=NP. Despite this result, we present two algorithms that have good performance for medium-size networks.

Download or read book Modeling Metabolism and Regulation to Facilitate Strain Characterization and Design written by Thomas Mueller and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational models of metabolism and regulation can provide insights into not onlyexisting cellular processes, but also serve as a platform for developing strain design strategies toachieve a desired goal. The work discussed here focuses on the development of models fororganisms with native capabilities that make them appealing candidates for industrial application,most notably cyanobacteria. Cyanobacteria are photosynthetic prokaryotes that have beenexplored for the production of a wide variety of compounds, but suffer from several drawbacks ascompared to existing industrial strains including a limited knowledgebase and slower growthrates. The first part of this dissertation focuses on expanding that knowledgebase through thedevelopment of genome-scale metabolic models for several model cyanobacteria and theintroduction of a semi-automated model generation workflow to expedite accurate modeldevelopment. This workflow is then applied to Synechococcus UTEX 2973, a fast growingcyanobacterium, in order to better understand possible causes for its fast-growth phenotype.The regulatory response of an organism to its environment is an important factor inunderstanding an organism. The second part of this dissertation targets the incorporation of geneexpression data into metabolic models to refine flux predictions, as well as the development ofregulatory networks for several cyanobacteria over the diurnal cycle. The CoreReg methodapplies additional constraints based on gene expression data on a genome-scale metabolic model,and allows for the identification of specific reactions, the effects of whose regulation propagatesthroughout the larger network. These reactions can be targeted to alleviate the effects of a stressoron the organisms metabolism. The creation of regulatory networks over the complete diurnalcycle facilitates the identification of transcription factors native to an organism that can becoopted to control other processes. This was done to select several transcription factors to control processes in the model cyanobacterium Synechocystis 6803 to accommodate the introduction ofnitrogen fixation.

Download or read book Control Theory and Systems Biology written by Pablo A. Iglesias and published by MIT Press. This book was released on 2010 with total page 359 pages. Available in PDF, EPUB and Kindle. Book excerpt: A survey of how engineering techniques from control and systems theory can be used to help biologists understand the behavior of cellular systems.

Download or read book Cell Culture Technology for Pharmaceutical and Cell Based Therapies written by Sadettin Ozturk and published by CRC Press. This book was released on 2005-08-30 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: Edited by two of the most distinguished pioneers in genetic manipulation and bioprocess technology, this bestselling reference presents a comprehensive overview of current cell culture technology used in the pharmaceutical industry. Contributions from several leading researchers showcase the importance of gene discovery and genomic technology devel

Download or read book Pyomo Optimization Modeling in Python written by William E. Hart and published by Springer Science & Business Media. This book was released on 2012-02-15 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a complete and comprehensive reference/guide to Pyomo (Python Optimization Modeling Objects) for both beginning and advanced modelers, including students at the undergraduate and graduate levels, academic researchers, and practitioners. The text illustrates the breadth of the modeling and analysis capabilities that are supported by the software and support of complex real-world applications. Pyomo is an open source software package for formulating and solving large-scale optimization and operations research problems. The text begins with a tutorial on simple linear and integer programming models. A detailed reference of Pyomo's modeling components is illustrated with extensive examples, including a discussion of how to load data from data sources like spreadsheets and databases. Chapters describing advanced modeling capabilities for nonlinear and stochastic optimization are also included. The Pyomo software provides familiar modeling features within Python, a powerful dynamic programming language that has a very clear, readable syntax and intuitive object orientation. Pyomo includes Python classes for defining sparse sets, parameters, and variables, which can be used to formulate algebraic expressions that define objectives and constraints. Moreover, Pyomo can be used from a command-line interface and within Python's interactive command environment, which makes it easy to create Pyomo models, apply a variety of optimizers, and examine solutions. The software supports a different modeling approach than commercial AML (Algebraic Modeling Languages) tools, and is designed for flexibility, extensibility, portability, and maintainability but also maintains the central ideas in modern AMLs.

Download or read book Real time Coastal Observing Systems for Marine Ecosystem Dynamics and Harmful Algal Blooms written by Babin, Marcel and published by UNESCO. This book was released on 2008-06-05 with total page 880 pages. Available in PDF, EPUB and Kindle. Book excerpt: The proliferation of harmful phytoplankton in marine ecosystems can cause massive fish kills, contaminate seafood with toxins, impact local and regional economies and dramatically affect ecological balance. Real-time observations are essential for effective short-term operational forecasting, but observation and modelling systems are still being developed. This volume provides guidance for developing real-time and near real-time sensing systems for observing and predicting plankton dynamics, including harmful algal blooms, in coastal waters. The underlying theory is explained and current trends in research and monitoring are discussed.Topics covered include: coastal ecosystems and dynamics of harmful algal blooms; theory and practical applications of in situ and remotely sensed optical detection of microalgal distributions and composition; theory and practical applications of in situ biological and chemical sensors for targeted species and toxin detection; integrated observing systems and platforms for detection; diagnostic and predictive modelling of ecosystems and harmful algal blooms, including data assimilation techniques; observational needs for the public and government; and future directions for research and operations.

Download or read book Nonlinear Dynamics and Chaos written by Steven H. Strogatz and published by CRC Press. This book was released on 2018-05-04 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook is aimed at newcomers to nonlinear dynamics and chaos, especially students taking a first course in the subject. The presentation stresses analytical methods, concrete examples, and geometric intuition. The theory is developed systematically, starting with first-order differential equations and their bifurcations, followed by phase plane analysis, limit cycles and their bifurcations, and culminating with the Lorenz equations, chaos, iterated maps, period doubling, renormalization, fractals, and strange attractors.