Download or read book Expanding the Applications of High throughput DNA Sequencing written by Jeffrey Alan Hussmann and published by . This book was released on 2015 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA sequencing is the process of determining the identities of the nucleotides that make up a molecule of DNA. The rapid pace of advancements in sequencing technologies in recent years have made it possible to simultaneously determine the sequences of hundreds of millions of short DNA fragments. The ability to perform sequencing with such high throughput has revolutionized the study of biological systems, but the types of questions that can be answered through sequencing-based experiments can be limited by the presence of different kinds of noise and biases in these experiments. One class of applications of high-throughput sequencing involves identifying genetic variation, such as finding rare mutations in the genomes of cancerous cells. In these applications, the sensitivity with which rare genetic variants can be detected is limited by the relatively high rate with which current DNA sequencing technologies incorrectly identify nucleotides. In the first half of this thesis, we present a method for dramatically reducing the rate at which these incorrect identifications occur. Our method, called circle sequencing, creates redundant copies of the sequence of each input molecule of DNA. This is accomplished by circularizing each DNA fragment and performing rolling circle amplification on these circles with a strand-displacing polymerase. The resulting products consist of several physically linked copies of the original sequence in each fragment. When these products are sequenced, this informational redundancy protects against random errors introduced during sequencing, allowing for highly accurate recovery of the original sequence of each input molecule. By eliminating the vast majority of incorrectly identified nucleotides from the resulting data, our method enables the sensitive detection of rare variants and opens up exciting new questions involving such variants to direct measurement by sequencing. An entirely different application of high-throughput sequencing is to selectively capture and sequence stretches of DNA or RNA that are participating in a process of interest within a cell. The accuracy of quantitative inferences made by this type of experiment can be severely impacted, however, by biases introduced during the experimental manipulations used to isolate biologically relevant fragments of DNA from cells. Ribosome profiling is an experimental technique that consists of sequencing short stretches of messenger RNAs that are protected from nuclease digestion by the presence of a bound ribosome. The resulting data represents millions of snapshots of the locations of actively translating ribosomes. In theory, these snapshots can be used to determine how long ribosomes take to translate each type of codon by quantifying how often ribosomes are observed positioned over that codon. In practice, different studies in yeast attempting to do this have reached contradictory and counterintuitive conclusions. In the second half of this thesis, we perform a large-scale comparative analysis of data from many different ribosome profiling experiments in order to resolve these contradictions. We identify a previously unappreciated source of systematic bias in a subset of these experiments. This bias prevents these experiments from accurately measuring ribosomes in proportion to how long they spend at each position in vivo. Understanding this bias provides insight into the true signatures of translation dynamics in yeast and offers important guidance for the future design and interpretation of sequencing-based approaches to measuring these dynamics.
Download or read book New High Throughput Technologies for DNA Sequencing and Genomics written by Keith R. Mitchelson and published by Elsevier. This book was released on 2011-09-22 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the independent invention of DNA sequencing by Sanger and by Gilbert 30 years ago, it has grown from a small scale technique capable of reading several kilobase-pair of sequence per day into today's multibillion dollar industry. This growth has spurred the development of new sequencing technologies that do not involve either electrophoresis or Sanger sequencing chemistries. Sequencing by Synthesis (SBS) involves multiple parallel micro-sequencing addition events occurring on a surface, where data from each round is detected by imaging. New High Throughput Technologies for DNA Sequencing and Genomics is the second volume in the Perspectives in Bioanalysis series, which looks at the electroanalytical chemistry of nucleic acids and proteins, development of electrochemical sensors and their application in biomedicine and in the new fields of genomics and proteomics. The authors have expertly formatted the information for a wide variety of readers, including new developments that will inspire students and young scientists to create new tools for science and medicine in the 21st century.Reviews of complementary developments in Sanger and SBS sequencing chemistries, capillary electrophoresis and microdevice integration, MS sequencing and applications set the framework for the book.* 'Hot Topic' with DNA sequencing continuing as a major research activity in many areas of life science and medicine.* Bringing together new developments in DNA sequencing technology* Reviewing issues relevant to the new applications used
Download or read book Bioinformatics for High Throughput Sequencing written by Naiara Rodríguez-Ezpeleta and published by Springer Science & Business Media. This book was released on 2011-10-26 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Next generation sequencing is revolutionizing molecular biology. Owing to this new technology it is now possible to carry out a panoply of experiments at an unprecedented low cost and high speed. These go from sequencing whole genomes, transcriptomes and small non-coding RNAs to description of methylated regions, identification protein – DNA interaction sites and detection of structural variation. The generation of gigabases of sequence information for each of this huge bandwidth of applications in just a few days makes the development of bioinformatics applications for next generation sequencing data analysis as urgent as challenging.
Download or read book Next Generation Sequencing written by Jerzy Kulski and published by BoD – Books on Demand. This book was released on 2016-01-14 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Next generation sequencing (NGS) has surpassed the traditional Sanger sequencing method to become the main choice for large-scale, genome-wide sequencing studies with ultra-high-throughput production and a huge reduction in costs. The NGS technologies have had enormous impact on the studies of structural and functional genomics in all the life sciences. In this book, Next Generation Sequencing Advances, Applications and Challenges, the sixteen chapters written by experts cover various aspects of NGS including genomics, transcriptomics and methylomics, the sequencing platforms, and the bioinformatics challenges in processing and analysing huge amounts of sequencing data. Following an overview of the evolution of NGS in the brave new world of omics, the book examines the advances and challenges of NGS applications in basic and applied research on microorganisms, agricultural plants and humans. This book is of value to all who are interested in DNA sequencing and bioinformatics across all fields of the life sciences.
Download or read book Development of Targeted High Throughput DNA Sequencing Methods and Their Application in Evolutionary Research written by Matthias Meyer and published by . This book was released on 2009 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book High Throughput Next Generation Sequencing written by Young Min Kwon and published by Humana Press. This book was released on 2011-03-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Due to their novel concepts and extraordinary high-throughput sequencing capacity, the “next generation sequencing” methods allow scientists to grasp system-wide landscapes of the complex molecular events taking place in various biological systems, including microorganisms and microbial communities. These methods are now being recognized as essential tools for a more comprehensive and deeper understanding of the mechanisms underlying many biological processes. In High-Throughput Next Generation Sequencing: Methods and Applications, experts in the field explore the most recent advances in the applications of next generation sequencing technologies with an emphasis on microorganisms and their communities; however, the methods described in this book will also offer general applications relevant to the study of any living organisms. Written in the highly successful Methods in Molecular BiologyTM 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. Comprehensive and cutting-edge, High-Throughput Next Generation Sequencing: Methods and Applications is an excellent collection of chapters to aid all scientists who wish to apply these innovative research tools to enhance their own pursuits in microbiology and also biology in general.
Download or read book Field Guidelines for Genetic Experimental Designs in High Throughput Sequencing written by Ana M. Aransay and published by Springer. This book was released on 2016-06-02 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: High throughput sequencing (HTS) technologies have conquered the genomics and epigenomics worlds. The applications of HTS methods are wide, and can be used to sequence everything from whole or partial genomes, transcriptomes, non-coding RNAs, ribosome profiling, to single-cell sequencing. Having such diversity of alternatives, there is a demand for information by research scientists without experience in HTS that need to choose the most suitable methodology or combination of platforms and to define their experimental designs to achieve their specific objectives. Field Guidelines for Genetic Experimental Designs in High-Throughput Sequencing aims to collect in a single volume all aspects that should be taken into account when HTS technologies are being incorporated into a research project and the reasons behind them. Moreover, examples of several successful strategies will be analyzed to make the point of the crucial features. This book will be of use to all scientist that are unfamiliar with HTS and want to incorporate such technologies to their research.
Download or read book Various Algorithms for High Throughput Sequencing written by Vladimir Yanovsky and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Encyclopedia of Bioinformatics and Computational Biology written by and published by Elsevier. This book was released on 2018-08-21 with total page 3421 pages. Available in PDF, EPUB and Kindle. Book excerpt: Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics, Three Volume Set combines elements of computer science, information technology, mathematics, statistics and biotechnology, providing the methodology and in silico solutions to mine biological data and processes. The book covers Theory, Topics and Applications, with a special focus on Integrative –omics and Systems Biology. The theoretical, methodological underpinnings of BCB, including phylogeny are covered, as are more current areas of focus, such as translational bioinformatics, cheminformatics, and environmental informatics. Finally, Applications provide guidance for commonly asked questions. This major reference work spans basic and cutting-edge methodologies authored by leaders in the field, providing an invaluable resource for students, scientists, professionals in research institutes, and a broad swath of researchers in biotechnology and the biomedical and pharmaceutical industries. Brings together information from computer science, information technology, mathematics, statistics and biotechnology Written and reviewed by leading experts in the field, providing a unique and authoritative resource Focuses on the main theoretical and methodological concepts before expanding on specific topics and applications Includes interactive images, multimedia tools and crosslinking to further resources and databases
Download or read book Human Genetics and Genomics written by Bruce R. Korf and published by John Wiley & Sons. This book was released on 2012-11-19 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: This fourth edition of the best-selling textbook, Human Genetics and Genomics, clearly explains the key principles needed by medical and health sciences students, from the basis of molecular genetics, to clinical applications used in the treatment of both rare and common conditions. A newly expanded Part 1, Basic Principles of Human Genetics, focuses on introducing the reader to key concepts such as Mendelian principles, DNA replication and gene expression. Part 2, Genetics and Genomics in Medical Practice, uses case scenarios to help you engage with current genetic practice. Now featuring full-color diagrams, Human Genetics and Genomics has been rigorously updated to reflect today’s genetics teaching, and includes updated discussion of genetic risk assessment, “single gene” disorders and therapeutics. Key learning features include: Clinical snapshots to help relate science to practice 'Hot topics' boxes that focus on the latest developments in testing, assessment and treatment 'Ethical issues' boxes to prompt further thought and discussion on the implications of genetic developments 'Sources of information' boxes to assist with the practicalities of clinical research and information provision Self-assessment review questions in each chapter Accompanied by the Wiley E-Text digital edition (included in the price of the book), Human Genetics and Genomics is also fully supported by a suite of online resources at www.korfgenetics.com, including: Factsheets on 100 genetic disorders, ideal for study and exam preparation Interactive Multiple Choice Questions (MCQs) with feedback on all answers Links to online resources for further study Figures from the book available as PowerPoint slides, ideal for teaching purposes The perfect companion to the genetics component of both problem-based learning and integrated medical courses, Human Genetics and Genomics presents the ideal balance between the bio-molecular basis of genetics and clinical cases, and provides an invaluable overview for anyone wishing to engage with this fast-moving discipline.
Download or read book Microbial Forensics written by Bruce Budowle and published by Academic Press. This book was released on 2010-10-27 with total page 753 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microbial Forensics is a rapidly evolving scientific discipline. In the last decade, and particularly due to the anthrax letter attacks in the United States, microbial forensics has become more formalized and has played an increasingly greater role in crime investigations. This has brought renewed interest, development and application of new technologies, and new rules of forensic and policy engagement. It has many applications ranging from biodefense, criminal investigations, providing intelligence information, making society more secure, and helping protect precious resources, particularly human life. A combination of diverse areas is investigated, including the major disciplines of biology, microbiology, medicine, chemistry, physics, statistics, population genetics, and computer science. Microbial Forensics, Second Edition is fully revised and updated and serves as a complete reference of the discipline. It describes the advances, as well as the challenges and opportunities ahead, and will be integral in applying science to help solve future biocrimes. - A collection of microbiology, virology, toxicology and mycology as it relates to forensics, in one reference - New and expanded content to include statistical analysis of forensic data and legal admissibility and the standards of evidence, to name a few - Includes research information and application of that research to crime scene analysis, which will allow practitioners to understand and apply the knowledge to their practice with ease
Download or read book Review of the Department of Energy s Genomics GTL Program written by National Research Council and published by National Academies Press. This book was released on 2006-04-19 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt: The U.S. Department of Energy (DOE) promotes scientific and technological innovation to advance the national, economic, and energy security of the United States. Recognizing the potential of microorganisms to offer new energy alternatives and remediate environmental contamination, DOE initiated the Genomes to Life program, now called Genomics: GTL, in 2000. The program aims to develop a predictive understanding of microbial systems that can be used to engineer systems for bioenergy production and environmental remediation, and to understand carbon cycling and sequestration. This report provides an evaluation of the program and its infrastructure plan. Overall, the report finds that GTL's research has resulted in and promises to deliver many more scientific advancements that contribute to the achievement of DOE's goals. However, the DOE's current plan for building four independent facilities for protein production, molecular imaging, proteome analysis, and systems biology sequentially may not be the most cost-effective, efficient, and scientifically optimal way to provide this infrastructure. As an alternative, the report suggests constructing up to four institute-like facilities, each of which integrates the capabilities of all four of the originally planned facility types and focuses on one or two of DOE's mission goals. The alternative infrastructure plan could have an especially high ratio of scientific benefit to cost because the need for technology will be directly tied to the biology goals of the program.
Download or read book Toward a More Accurate Genome written by William Jacob Benhardt Biesinger and published by . This book was released on 2014 with total page 124 pages. Available in PDF, EPUB and Kindle. Book excerpt: High-throughput sequencing enables basic and translational biology to query the mechanics of both life and disease at single-nucleotide resolution and with breadth that spans the genome. This revolutionary technology is a major tool in biomedical research, impacting our understanding of life's most basic mechanics and affecting human health and medicine. Unfortunately, this important technology produces very large, error-prone datasets that require substantial computational processing before experimental conclusions can be made. Since errors and hidden biases in the data may influence empirically-derived conclusions, accurate algorithms and models of the data are critical. This thesis focuses on the development of statistical models for high-throughput sequencing data which are capable of handling errors and which are built to reflect biological realities. First, we focus on increasing the fraction of the genome that can be reliably queried in biological experiments using high-throughput sequencing methods by expanding analysis into repeat regions of the genome. The method allows partial observation of the gene regulatory network topology through identification of transcription factor binding sites using Chromatin Immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Binding site clustering, or "peak-calling", can be frustrated by the complex, repetitive nature of genomes. Traditionally, these regions are censored from any interpretation, but we re-enable their interpretation using a probabilistic method for realigning problematic DNA reads. Second, we leverage high-throughput sequencing data for the empirical discovery of underlying epigenetic cell state, enabled through analysis of combinations of histone marks. We use a novel probabilistic model to perform spatial and temporal clustering of histone marks and capture mark combinations that correlate well with cell activity. A first in epigenetic modeling with high-throughput sequencing data, we not only pool information across cell types, but directly model the relationship between them, improving predictive power across several datasets. Third, we develop a scalable approach to genome assembly using high-throughput sequencing reads. While several assembly solutions exist, most don't scale well to large datasets, requiring computers with copious memory to assemble large genomes. Throughput continues to increase and the large datasets available today and in the near future will require truly scalable methods. We present a promising distributed method for genome assembly which distributes the de Bruijn graph across many computers and seamlessly spills to disk when main memory is insufficient. We also show novel graph cleaning algorithms which should handle increased errors from large datasets better than traditional graph structure-based cleaning. High-throughput sequencing plays an important role in biomedical research, and has already affected human health and medicine. Future experimental procedures will continue to rely on statistical methods to provide crucial error and bias correction, in addition to modeling expected outcomes. Thus, further development of robust statistical models is critical to the future high-throughput sequencing, ensuring a strong foundation for correct biological conclusions.
Download or read book Mapping and Sequencing the Human Genome written by National Research Council and published by National Academies Press. This book was released on 1988-01-01 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is growing enthusiasm in the scientific community about the prospect of mapping and sequencing the human genome, a monumental project that will have far-reaching consequences for medicine, biology, technology, and other fields. But how will such an effort be organized and funded? How will we develop the new technologies that are needed? What new legal, social, and ethical questions will be raised? Mapping and Sequencing the Human Genome is a blueprint for this proposed project. The authors offer a highly readable explanation of the technical aspects of genetic mapping and sequencing, and they recommend specific interim and long-range research goals, organizational strategies, and funding levels. They also outline some of the legal and social questions that might arise and urge their early consideration by policymakers.
Download or read book Applications in High throughput Sequencing Technologies written by Paul Macaraeg Rigor and published by . This book was released on 2015 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt: High-throughput sequencing (HTS) technologies play important roles in the life sciences by allowing the rapid parallel sequencing of very large numbers of relatively short nucleotide sequences, in applications ranging from genome sequencing and resequencing to digital microarrays and ChIP-Seq experiments. As experiments scale up, HTS technologies create new bioinformatics challenges for the storage, distribution, and downstream analyses of HTS data. In this thesis, we address the challenges and opportunities in the storage and downstream analyses of data derived from HTS technologies.To address the growing amount of HTS data, we develop data structures and compression algorithms for HTS data storage. A processing stage maps short sequences to a reference genome or a large table of sequences. Then the integers representing the short sequence absolute or relative addresses, their length, and the substitutions they may contain are compressed and stored using various entropy coding algorithms, including both old and new fixed codes (e.g Golomb, Elias Gamma, MOV) and variable codes (e.g. Huffman). The general methodology is illustrated and applied to several HTS data sets. Results show that the information contained in HTS files can be compressed by a factor of 10 or more, depending on the statistical properties of the data sets and various other choices and constraints. Our algorithms fair well against general purpose compression programs such as gzip, bzip2 and 7zip; timing results show that our algorithms are consistently faster than the best general purpose compression programs.Achieving a comprehensive map of all the regulatory elements encoded in the human genome is a fundamental challenge of biomedical research. So far, only a small fraction of the regulatory elements have been characterized, and there is great interest in applying computational techniques to systematically discover these elements. Such efforts, however, have been significantly hindered by the overwhelming size of non-coding DNA regions and the statistical variability and complex spatial organizations of mammalian regulatory elements. The MotifMap system uses databases of transcription factor binding motifs, refined genome alignments, and a comparative genomic statistical approach to provide comprehensive maps of candidate regulatory elements encoded in the genomes of model species.MotifMap and its integration with other data provide a foundation for analyzing gene regulation on a genome-wide scale, and for automatically generating regulatory pathways and hypotheses. The power of this approach is demonstrated and discussed using the P53 apoptotic pathway and the Gli hedgehog pathways as examples.Further application of MotifMap is underlined by its integration into CircadiOmics (developed in the Baldi lab), which aims to decode transcriptional machinery that are under circadian control. Here we utilize MotifMap in understanding and delineating the roles of a subset of the sirtuin family of deacetylases in regulating circadian rhythms. Circadian rhythms are intimately linked to cellular metabolism. Specifically, the NAD+-dependent deacetylase SIRT1, the founding member of the sirtuin family, contributes to clock function. Whereas SIRT1 exhibits diversity in deacetylation targets and subcellular localization, SIRT6 is the only constitutively chromatin-associated sirtuin and is prominently present at transcriptionally active genomic loci. Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity and therefore define distinctly partitioned classes of circadian genes. SIRT6 interacts with CLOCK:BMAL1 and, differently from SIRT1, governs their chromatin recruitment to circadian gene promoters. Moreover, SIRT6 controls circadian chromatin recruitment of SREBP-1, resulting in the cyclic regulation of genes implicated in fatty acid and cholesterol metabolism. This mechanism parallels a phenotypic disruption in fatty acid metabolism in SIRT6 null mice as revealed by circadian metabolome analyses. Thus, genomic partitioning by two independent sirtuins contributes to differential control of circadian metabolism.
Download or read book Molecular Structure of Nucleic Acids written by and published by Ardent Media. This book was released on 1953 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Clinical Applications for Next Generation Sequencing written by Urszula Demkow and published by Academic Press. This book was released on 2015-09-10 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: Clinical Applications for Next Generation Sequencing provides readers with an outstanding postgraduate resource to learn about the translational use of NGS in clinical environments. Rooted in both medical genetics and clinical medicine, the book fills the gap between state-of-the-art technology and evidence-based practice, providing an educational opportunity for users to advance patient care by transferring NGS to the needs of real-world patients. The book builds an interface between genetic laboratory staff and clinical health workers to not only improve communication, but also strengthen cooperation. Users will find valuable tactics they can use to build a systematic framework for understanding the role of NGS testing in both common and rare diseases and conditions, from prenatal care, like chromosomal abnormalities, up to advanced age problems like dementia. - Fills the gap between state-of-the-art technology and evidence-based practice - Provides an educational opportunity which advances patient care through the transfer of NGS to real-world patient assessment - Promotes a practical tool that clinicians can apply directly to patient care - Includes a systematic framework for understanding the role of NGS testing in many common and rare diseases - Presents evidence regarding the important role of NGS in current diagnostic strategies
