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Author: Zuyi Huang
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Mathematical models of signal transduction pathways are characterized by a large number of proteins and uncertain parameters, yet only a limited amount of quantitative data is available. The dissertation addresses this problem using two different approaches: the first approach deals with a model simplification procedure for signaling pathways that reduces the model size but retains the physical interpretation of the remaining states, while the second approach deals with creating rich data sets by computing transcription factor profiles from fluorescent images of green-fluorescent-protein (GFP) reporter cells. For the first approach a model simplification procedure for signaling pathway models is presented. The technique makes use of sensitivity and observability analysis to select the retained proteins for the simplified model. The presented technique is applied to an IL-6 signaling pathway model. It is found that the model size can be significantly reduced and the simplified model is able to adequately predict the dynamics of key proteins of the signaling pathway. An approach for quantitatively determining transcription factor profiles from GFP reporter data is developed as the second major contribution of this work. The procedure analyzes fluorescent images to determine fluorescence intensity profiles using principal component analysis and K-means clustering, and then computes the transcription factor concentration from the fluorescence intensity profiles by solving an inverse problem involving a model describing transcription, translation, and activation of green fluorescent proteins. Activation profiles of the transcription factors NF-kB, nuclear STAT3, and C/EBPß are obtained using the presented approach. The data for NF-kB is used to develop a model for TNF-a signal transduction while the data for nuclear STAT3 and C/EBPß is used to verify the simplified IL-6 model. Finally, an approach is developed to compute the distribution of transcription factor profiles among a population of cells. This approach consists of an algorithm for identifying individual fluorescent cells from fluorescent images, and an algorithm to compute the distribution of transcription factor profiles from the fluorescence intensity distribution by solving an inverse problem. The technique is applied to experimental data to derive the distribution of NF-kB concentrations from fluorescent images of a NF-kB GFP reporter system.
Author: Zuyi Huang
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Mathematical models of signal transduction pathways are characterized by a large number of proteins and uncertain parameters, yet only a limited amount of quantitative data is available. The dissertation addresses this problem using two different approaches: the first approach deals with a model simplification procedure for signaling pathways that reduces the model size but retains the physical interpretation of the remaining states, while the second approach deals with creating rich data sets by computing transcription factor profiles from fluorescent images of green-fluorescent-protein (GFP) reporter cells. For the first approach a model simplification procedure for signaling pathway models is presented. The technique makes use of sensitivity and observability analysis to select the retained proteins for the simplified model. The presented technique is applied to an IL-6 signaling pathway model. It is found that the model size can be significantly reduced and the simplified model is able to adequately predict the dynamics of key proteins of the signaling pathway. An approach for quantitatively determining transcription factor profiles from GFP reporter data is developed as the second major contribution of this work. The procedure analyzes fluorescent images to determine fluorescence intensity profiles using principal component analysis and K-means clustering, and then computes the transcription factor concentration from the fluorescence intensity profiles by solving an inverse problem involving a model describing transcription, translation, and activation of green fluorescent proteins. Activation profiles of the transcription factors NF-kB, nuclear STAT3, and C/EBPß are obtained using the presented approach. The data for NF-kB is used to develop a model for TNF-a signal transduction while the data for nuclear STAT3 and C/EBPß is used to verify the simplified IL-6 model. Finally, an approach is developed to compute the distribution of transcription factor profiles among a population of cells. This approach consists of an algorithm for identifying individual fluorescent cells from fluorescent images, and an algorithm to compute the distribution of transcription factor profiles from the fluorescence intensity distribution by solving an inverse problem. The technique is applied to experimental data to derive the distribution of NF-kB concentrations from fluorescent images of a NF-kB GFP reporter system.
Author: James E. Ferrell
Publisher: Garland Science
ISBN: 1000430782
Category : Science
Languages : en
Pages : 391
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Book Description
How can we understand the complexity of genes, RNAs, and proteins and the associated regulatory networks? One approach is to look for recurring types of dynamical behavior. Mathematical models prove to be useful, especially models coming from theories of biochemical reactions such as ordinary differential equation models. Clever, careful experiments test these models and their basis in specific theories. This textbook aims to provide advanced students with the tools and insights needed to carry out studies of signal transduction drawing on modeling, theory, and experimentation. Early chapters summarize the basic building blocks of signaling systems: binding/dissociation, synthesis/destruction, and activation/inactivation. Subsequent chapters introduce various basic circuit devices: amplifiers, stabilizers, pulse generators, switches, stochastic spike generators, and oscillators. All chapters consistently use approaches and concepts from chemical kinetics and nonlinear dynamics, including rate-balance analysis, phase plane analysis, nullclines, linear stability analysis, stable nodes, saddles, unstable nodes, stable and unstable spirals, and bifurcations. This textbook seeks to provide quantitatively inclined biologists and biologically inclined physicists with the tools and insights needed to apply modeling and theory to interesting biological processes. Key Features: · Full-color illustration program with diagrams to help illuminate the concepts · Enables the reader to apply modeling and theory to the biological processes · Further Reading for each chapter · High-quality figures available for instructors to download
Author: Aleš Prokop
Publisher: Springer Science & Business Media
ISBN: 9400768036
Category : Medical
Languages : en
Pages : 569
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Book Description
Growth in the pharmaceutical market has slowed down – almost to a standstill. One reason is that governments and other payers are cutting costs in a faltering world economy. But a more fundamental problem is the failure of major companies to discover, develop and market new drugs. Major drugs losing patent protection or being withdrawn from the market are simply not being replaced by new therapies – the pharmaceutical market model is no longer functioning effectively and most pharmaceutical companies are failing to produce the innovation needed for success. This multi-authored new book looks at a vital strategy which can bring innovation to a market in need of new ideas and new products: Systems Biology (SB). Modeling is a significant task of systems biology. SB aims to develop and use efficient algorithms, data structures, visualization and communication tools to orchestrate the integration of large quantities of biological data with the goal of computer modeling. It involves the use of computer simulations of biological systems, such as the networks of metabolites comprise signal transduction pathways and gene regulatory networks to both analyze and visualize the complex connections of these cellular processes. SB involves a series of operational protocols used for performing research, namely a cycle composed of theoretical, analytic or computational modeling to propose specific testable hypotheses about a biological system, experimental validation, and then using the newly acquired quantitative description of cells or cell processes to refine the computational model or theory.
Author: Nils Blüthgen
Publisher:
ISBN: 9783832513467
Category :
Languages : en
Pages : 0
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Book Description
The analysis of complex intra-cellular signal transduction pathways involving reversible protein modifications and gene regulation requires a mixture of novel experimental and theoretical methods, often characterised as a "systems-biological approach". Mathematical modelling of the dynamics of the dynamics often determines the cellular response. This book gives an overview about existing models and develops new models and methods to investigate signalling pathways downstream of the oncogene Ras. It pays special attention to the MAPK signal transduction cascade, which has been subject of mathematical modelling for over a decade. In the first part the stimulus-response curve of the MAPK cascade is characterised both mathematically and experimentally. First, previous results are reviewed and the effect of feedback loops on the dynamics of the cascade is discussed. Subsequently, the effect of sequestration due to high enzyme concentrations as they are present in this pathway is discussed. Then, it is investigated whether the activation is bistable. In the second part the gene expression changes due to Ras-mediated signalling are investigated. First, expression time-series of well-defined target genes after induction of oncogenic Ras are investigated, and a mathematical model of a feedback via the transcriptional induction of a phosphatase is derived. Second, a method is developed to functionally classify targets genes. Finally, this method is extended to allow for functional prediction of transcription factor targets.
Author: Sangdun Choi
Publisher: Springer Science & Business Media
ISBN: 1441957979
Category : Science
Languages : en
Pages : 900
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Book Description
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.
Author: Lilia Alberghina
Publisher: Springer Science & Business Media
ISBN: 9783540742692
Category : Computers
Languages : en
Pages : 432
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Book Description
For life to be understood and disease to become manageable, the wealth of postgenomic data now needs to be made dynamic. This development requires systems biology, integrating computational models for cells and organisms in health and disease; quantitative experiments (high-throughput, genome-wide, living cell, in silico); and new concepts and principles concerning interactions. This book defines the new field of systems biology and discusses the most efficient experimental and computational strategies. The benefits for industry, such as the new network-based drug-target design validation, and testing, are also presented.
Author: Lan K. Nguyen
Publisher: Springer Nature
ISBN: 1071630083
Category : Science
Languages : en
Pages : 387
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Book Description
This volume focuses on the computational modeling of cell signaling networks and the application of these models and model-based analysis to systems and personalized medicine. Chapters guide readers through various modeling approaches for signaling networks, new methods and techniques that facilitate model development and analysis, and new applications of signaling network modeling towards systems and personalized treatment of cancer. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and methods, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Computational Modeling of Signaling Networks aims to benefit a wide spectrum of readers including researchers from the biological as well as computational systems biology communities.
Author: Andreas Kremling
Publisher: CRC Press
ISBN: 1466567899
Category : Mathematics
Languages : en
Pages : 382
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Book Description
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.
Author: Akhilesh Pandey
Publisher: Springer Verlag
ISBN: 9781588294876
Category : Science
Languages : en
Pages : 350
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Book Description
Signal Transduction: A Systems Biology Approach presents readers with an introduction to systems biology as well as to provide details of approaches and methods in use today to study signal transduction from a systems biology perspective. This text takes DNA microarrays, proteomics methods and in vivo methods and discusses them individually along with other chapters that will synthesize how the information derived from these methods can be more effectively utilized and integrated.
Author: Corrado Priami
Publisher: Springer Science & Business Media
ISBN: 364204185X
Category : Computers
Languages : en
Pages : 343
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Book Description
This issue on Computational Models for Cell Processes is based on a workshop that took place in Turku, Finland, May 2008. The papers span a mix of approaches to systems biology, ranging from quantitative techniques to computing paradigms inspired by biology.
