Quantitative Modeling and Statistical Analysis of Protein-DNA Binding Sites PDF Download
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Author: Matthias Siebert
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Matthias Siebert
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Yue Zhao
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 113
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Book Description
Organisms must control their gene expression to properly respond to developmental, stress or other environmental cues. A key part of this process is transcriptional regulation, which is largely accomplished by a complex network of transcription factor proteins (TFs) interact with their specific binding sites in the genome. Understanding how TFs select correct binding sites out of the vast number of potential binding sites in the genome is a key challenge in molecular biology. Recently, unprecedented amount of quantitative binding data have become available as results of developments in high-throughput experimental techniques. However, interpretation of high-throughput binding data has proved to be controversial, largely due to the lack of physically principled data analysis methods. ii An important question in the analysis of binding data is the complexity of the specificity model needed. This has important implications for both the characterization of specificity and for the prediction of the consequences of mutations. Structurally, TF-DNA interactions are complex with a wide variety of interactions between the protein and DNA making a simple recognition code impossible. Energetically, however, the situation may be much simpler. Detailed studies of a handful of TFs have shown that individual base pairs often contribute independently to the total binding energy. This view of simplicity has been challenged by data from high-throughput binding experiments, although the extent to which the sample model breaks down is uncertain due to lack of rigorous analysis methods. The goal of this thesis is to assess the complexity of model required to accurately represent TF specificity. To this end, I have developed a new statistical analysis method BEEML (Binding Energy Estimation by Maximum Likelihood) that parameterizes models of TF specificity from high-throughput quantitative binding data, using a realistic biophysical model. Employing the BEEML method, I show that the energetics of most TF-DNA interactions are simple, with bases in the binding site contribute approximately independently to the total binding energy. Further, I show that interactions in the binding site occur mostly between adjacent positions.
Author: George Locke
Publisher:
ISBN:
Category : DNA-binding proteins
Languages : en
Pages : 136
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Author: Harald Seitz
Publisher: Springer Science & Business Media
ISBN: 3540481478
Category : Medical
Languages : en
Pages : 212
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With contributions by numerous experts
Author: William Bialek
Publisher: Princeton University Press
ISBN: 1400845572
Category : Science
Languages : en
Pages : 653
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Book Description
A physicist's guide to the phenomena of life Interactions between the fields of physics and biology reach back over a century, and some of the most significant developments in biology—from the discovery of DNA's structure to imaging of the human brain—have involved collaboration across this disciplinary boundary. For a new generation of physicists, the phenomena of life pose exciting challenges to physics itself, and biophysics has emerged as an important subfield of this discipline. Here, William Bialek provides the first graduate-level introduction to biophysics aimed at physics students. Bialek begins by exploring how photon counting in vision offers important lessons about the opportunities for quantitative, physics-style experiments on diverse biological phenomena. He draws from these lessons three general physical principles—the importance of noise, the need to understand the extraordinary performance of living systems without appealing to finely tuned parameters, and the critical role of the representation and flow of information in the business of life. Bialek then applies these principles to a broad range of phenomena, including the control of gene expression, perception and memory, protein folding, the mechanics of the inner ear, the dynamics of biochemical reactions, and pattern formation in developing embryos. Featuring numerous problems and exercises throughout, Biophysics emphasizes the unifying power of abstract physical principles to motivate new and novel experiments on biological systems. Covers a range of biological phenomena from the physicist's perspective Features 200 problems Draws on statistical mechanics, quantum mechanics, and related mathematical concepts Includes an annotated bibliography and detailed appendixes
Author: Ron D. Appel
Publisher: World Scientific
ISBN: 9812838783
Category : Science
Languages : en
Pages : 464
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Book Description
Biological research and recent technological advances have resulted in an enormous increase in research data that require large storage capacities, powerful computing resources, and accurate data analysis algorithms. Bioinformatics is the field that provides these resources to life science researchers. The Swiss Institute of Bioinformatics (SIB), which has celebrated its 10th anniversary in 2008, is an institution of national importance, recognized worldwide for its state-of-the-art work. Organized as a federation of bioinformatics research groups from Swiss universities and research institutes, the SIB provides services to the life science community that are highly appreciated worldwide, and coordinates research and education in bioinformatics nationwide. The SIB plays a central role in life science research both in Switzerland and abroad by developing extensive and high-quality bioinformatics resources that are essential for all life scientists. Knowledge developed by SIB members in areas such as genomics, proteomics, and systems biology is directly transformed by academia and industry into innovative solutions to improve global health. Such an astounding concentration of talent in a given field is unusual and unique in Switzerland. This book provides an insight into some of the key areas of activity in bioinformatics in Switzerland. With contributions from SIB members, it covers both research work and major infrastructure efforts in genome and gene expression analysis, investigations on proteins and proteomes, evolutionary bioinformatics, and modeling of biological systems.
Author: Anand R. Asthagiri
Publisher: Academic Press
ISBN: 0123884039
Category : Computers
Languages : en
Pages : 427
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Book Description
Computational methods are playing an ever increasing role in cell biology. This volume of Methods in Cell Biology focuses on Computational Methods in Cell Biology and consists of two parts: (1) data extraction and analysis to distill models and mechanisms, and (2) developing and simulating models to make predictions and testable hypotheses. Focuses on computational methods in cell biology Split into 2 parts--data extraction and analysis to distill models and mechanisms, and developing and simulating models to make predictions and testable hypotheses Emphasizes the intimate and necessary connection with interpreting experimental data and proposing the next hypothesis and experiment
Author: Isidore Rigoutsos
Publisher: Oxford University Press
ISBN: 0190293764
Category : Science
Languages : en
Pages : 336
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Book Description
The advent of genome sequencing and associated technologies has transformed biologists' ability to measure important classes of molecules and their interactions. This expanded cellular view has opened the field to thousands of interactions that previously were outside the researchers' reach. The processing and interpretation of these new vast quantities of interconnected data call for sophisticated mathematical models and computational methods. Systems biology meets this need by combining genomic knowledge with theoretical, experimental and computational approaches from a number of traditional scientific disciplines to create a mechanistic explanation of cellular systems and processes. Systems Biology I: Genomics and Systems Biology II: Networks, Models, and Applications offer a much-needed study of genomic principles and their associated networks and models. Written for a wide audience, each volume presents a timely compendium of essential information that is necessary for a comprehensive study of the subject. The chapters in the two volumes reflect the hierarchical nature of systems biology. Chapter authors-world-recognized experts in their fields-provide authoritative discussions on a wide range of topics along this hierarchy. Volume I explores issues pertaining to genomics that range from prebiotic chemistry to noncoding RNAs. Volume II covers an equally wide spectrum, from mass spectrometry to embryonic stem cells. The two volumes are meant to provide a reliable reference for students and researchers alike.
Author: Phoebe A. Rice
Publisher: Royal Society of Chemistry
ISBN: 0854042725
Category : Science
Languages : en
Pages : 417
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Book Description
This book provides both in-depth background and up-to-date information in this area. The chapters are organized by general themes and principles, written by experts who illustrate topics with current findings. Topics covered include: - the role of ions and hydration in protein-nucleic acid interactions - transcription factors and combinatorial specificity - indirect readout of DNA sequence - single-stranded nucleic acid binding proteins - nucleic acid junctions and proteins, - RNA protein recognition - recognition of DNA damage. It will be a key reference for both advanced students and established scientists wishing to broaden their horizons.
Author: Gary Stormo
Publisher:
ISBN: 9781936113491
Category : Science
Languages : en
Pages : 198
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Book Description
One of the foundations of molecular biology is how the interactions of proteins with DNA control many aspects of gene expression. Since the mid-20th century discoveries of the lac repressor and operator and the competition between the cI and cro proteins for the same segment of DNA, we have learned an enormous amount about the interactions of proteins with DNA and their control of fundamental processes in the cell. Introduction to Protein-DNA Interactions: Structure, Thermodynamics, and Bioinformatics describes what we know about protein-DNA interactions from the complementary perspectives of molecular and structural biology and bioinformatics and how each perspective informs the others. A particular emphasis is on how insights from experimental work can be translated into specific computational approaches to create unified view of the field and a fuller understanding of protein-DNA interactions.
