Statistical Methods For High Dimensional Spatially Distributed Microbiome Data From Next Generation Sequencing

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Biostatistics for Human Genetic Epidemiology

Author : Bertram K. C. Chan
Publisher : Springer
ISBN 13 : 331993791X
Total Pages : 368 pages
Book Rating : 4.3/5 (199 download)

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Book Synopsis Biostatistics for Human Genetic Epidemiology by : Bertram K. C. Chan

Download or read book Biostatistics for Human Genetic Epidemiology written by Bertram K. C. Chan and published by Springer. This book was released on 2018-10-24 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book illustrates how biostatistics may numerically summarize human genetic epidemiology using R, and may be used successfully to solve problems in quantitative Genetic Epidemiology Biostatistics for Human Genetic Epidemiology provides statistical methodologies and R recipes for human genetic epidemiologic problems. It begins by introducing all the necessary probabilistic and statistical foundations, before moving on to topics related human genetic epidemiology, with R codes illustrations for various examples. This clear and concise book covers human genetic epidemiology, using R in data analysis, including multivariate data analysis. It examines probabilistic and statistical theories for modeling human genetic epidemiology – leading the readers through an effective epidemiologic model, from simple to advanced levels. Classical mathematical, probabilistic, and statistical theory are thoroughly discussed and presented. This book also presents R as a calculator and using R in data analysis. Additionally, it covers Advanced Human Genetic Data Concepts, the Study of Human Genetic Variation, Manhattan Plots, as well as the Procedures for Multiple Comparison. Numerous Worked Examples are provided for illustrations of concepts and real-life applications. Biostatistics for Human Genetic Epidemiology is an ideal reference for professionals and students in Medicine (particularly in Preventive Medicine and Public Health Medical Practices), as well as in Genetics, Epidemiology, and Biostatistics.

Compositional Data Analysis

Author : Vera Pawlowsky-Glahn
Publisher : John Wiley & Sons
ISBN 13 : 0470711353
Total Pages : 405 pages
Book Rating : 4.4/5 (77 download)

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Book Synopsis Compositional Data Analysis by : Vera Pawlowsky-Glahn

Download or read book Compositional Data Analysis written by Vera Pawlowsky-Glahn and published by John Wiley & Sons. This book was released on 2011-09-19 with total page 405 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is difficult to imagine that the statistical analysis of compositional data has been a major issue of concern for more than 100 years. It is even more difficult to realize that so many statisticians and users of statistics are unaware of the particular problems affecting compositional data, as well as their solutions. The issue of ``spurious correlation'', as the situation was phrased by Karl Pearson back in 1897, affects all data that measures parts of some whole, such as percentages, proportions, ppm and ppb. Such measurements are present in all fields of science, ranging from geology, biology, environmental sciences, forensic sciences, medicine and hydrology. This book presents the history and development of compositional data analysis along with Aitchison's log-ratio approach. Compositional Data Analysis describes the state of the art both in theoretical fields as well as applications in the different fields of science. Key Features: Reflects the state-of-the-art in compositional data analysis. Gives an overview of the historical development of compositional data analysis, as well as basic concepts and procedures. Looks at advances in algebra and calculus on the simplex. Presents applications in different fields of science, including, genomics, ecology, biology, geochemistry, planetology, chemistry and economics. Explores connections to correspondence analysis and the Dirichlet distribution. Presents a summary of three available software packages for compositional data analysis. Supported by an accompanying website featuring R code. Applied scientists working on compositional data analysis in any field of science, both in academia and professionals will benefit from this book, along with graduate students in any field of science working with compositional data.

Comprehensive Toxicology

Author :
Publisher : Elsevier
ISBN 13 : 0081006128
Total Pages : 8639 pages
Book Rating : 4.0/5 (81 download)

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Book Synopsis Comprehensive Toxicology by :

Download or read book Comprehensive Toxicology written by and published by Elsevier. This book was released on 2017-12-01 with total page 8639 pages. Available in PDF, EPUB and Kindle. Book excerpt: Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts

Ecological Diversity and Its Measurement

Author : Anne E. Magurran
Publisher : Springer Science & Business Media
ISBN 13 : 9401573581
Total Pages : 180 pages
Book Rating : 4.4/5 (15 download)

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Book Synopsis Ecological Diversity and Its Measurement by : Anne E. Magurran

Download or read book Ecological Diversity and Its Measurement written by Anne E. Magurran and published by Springer Science & Business Media. This book was released on 2013-04-17 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although diversity is one of the central themes of ecology there is considerable disagreement ab out how it should be measured. I first encountered this problem 10 ycars ago whcn I started my research career and spent a long time pouring ovcr the literature in order to find the most useful techniques. The intervening decade has seen a further increasc in the number ofpapers devoted to the topic of ecological diversity but has led to no consensus on how it should be measured. My aim in writing this book is therefore to provide a practical guide to ecological diversity and its measurement. In a quantitative subject such as the measurement of diversity it is inevitable that some mathematics are involved, but at all times these are kept as simple as possible, and the emphasis is constantly on ecological reality and practical application. I hope that others ente ring thc fascinating ficld of ecological diversity will find it hclpful. This book grew out of my work in The School of Biological and Environmental Studies at the New University ofUlster, Coleraine, Northern Ircland. I am indebted to all the ecologists there for pro vi ding a stimulating atmosphere. Foremost among these were Amyan Macfadyen and Palmer Newbould. A number of the figures and tables in the book are based on data collected in Northern Irish woodlands.

Microbial Forensics

Author : Bruce Budowle
Publisher : Academic Press
ISBN 13 : 0123820073
Total Pages : 753 pages
Book Rating : 4.1/5 (238 download)

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Book Synopsis Microbial Forensics by : Bruce Budowle

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

Oceanography and Benthic Ecology of Patagonian Fjords - 500 years From the Discovery of the Strait Magellan

Author : Giorgio Bavestrello
Publisher : Frontiers Media SA
ISBN 13 : 2889768899
Total Pages : 263 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Oceanography and Benthic Ecology of Patagonian Fjords - 500 years From the Discovery of the Strait Magellan by : Giorgio Bavestrello

Download or read book Oceanography and Benthic Ecology of Patagonian Fjords - 500 years From the Discovery of the Strait Magellan written by Giorgio Bavestrello and published by Frontiers Media SA. This book was released on 2022-09-02 with total page 263 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Evolution of Translational Omics

Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309224187
Total Pages : 354 pages
Book Rating : 4.3/5 (92 download)

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Book Synopsis Evolution of Translational Omics by : Institute of Medicine

Download or read book Evolution of Translational Omics written by Institute of Medicine and published by National Academies Press. This book was released on 2012-09-13 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.

The Lung Microbiome

Author : Michael J. Cox
Publisher : European Respiratory Society
ISBN 13 : 1849841020
Total Pages : 261 pages
Book Rating : 4.8/5 (498 download)

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Book Synopsis The Lung Microbiome by : Michael J. Cox

Download or read book The Lung Microbiome written by Michael J. Cox and published by European Respiratory Society. This book was released on 2019-03-01 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: Studying the lung microbiome requires a specialist approach to sampling, laboratory techniques and statistical analysis. This Monograph introduces the techniques used and discusses how respiratory sampling, 16S rRNA gene sequencing, metagenomics and the application of ecological theory can be used to examine the respiratory microbiome. It examines the different components of the respiratory microbiome: viruses and fungi in addition to the more frequently studied bacteria. It also considers a range of contexts from the paediatric microbiome and how this develops to disease of all ages including asthma and chronic obstructive pulmonary disease, chronic suppurative lung diseases, interstitial lung diseases, acquired pneumonias, transplantation, cancer and HIV, and the interaction of the respiratory microbiome and the environment.

Microbiomes of the Built Environment

Author : National Academies of Sciences, Engineering, and Medicine
Publisher : National Academies Press
ISBN 13 : 0309449839
Total Pages : 318 pages
Book Rating : 4.3/5 (94 download)

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Book Synopsis Microbiomes of the Built Environment by : National Academies of Sciences, Engineering, and Medicine

Download or read book Microbiomes of the Built Environment written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2017-10-06 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: People's desire to understand the environments in which they live is a natural one. People spend most of their time in spaces and structures designed, built, and managed by humans, and it is estimated that people in developed countries now spend 90 percent of their lives indoors. As people move from homes to workplaces, traveling in cars and on transit systems, microorganisms are continually with and around them. The human-associated microbes that are shed, along with the human behaviors that affect their transport and removal, make significant contributions to the diversity of the indoor microbiome. The characteristics of "healthy" indoor environments cannot yet be defined, nor do microbial, clinical, and building researchers yet understand how to modify features of indoor environmentsâ€"such as building ventilation systems and the chemistry of building materialsâ€"in ways that would have predictable impacts on microbial communities to promote health and prevent disease. The factors that affect the environments within buildings, the ways in which building characteristics influence the composition and function of indoor microbial communities, and the ways in which these microbial communities relate to human health and well-being are extraordinarily complex and can be explored only as a dynamic, interconnected ecosystem by engaging the fields of microbial biology and ecology, chemistry, building science, and human physiology. This report reviews what is known about the intersection of these disciplines, and how new tools may facilitate advances in understanding the ecosystem of built environments, indoor microbiomes, and effects on human health and well-being. It offers a research agenda to generate the information needed so that stakeholders with an interest in understanding the impacts of built environments will be able to make more informed decisions.

Statistical Analysis of Next Generation Sequencing Data

Author : Somnath Datta
Publisher : Springer
ISBN 13 : 3319072129
Total Pages : 438 pages
Book Rating : 4.3/5 (19 download)

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Book Synopsis Statistical Analysis of Next Generation Sequencing Data by : Somnath Datta

Download or read book Statistical Analysis of Next Generation Sequencing Data written by Somnath Datta and published by Springer. This book was released on 2014-07-03 with total page 438 pages. Available in PDF, EPUB and Kindle. Book excerpt: Next Generation Sequencing (NGS) is the latest high throughput technology to revolutionize genomic research. NGS generates massive genomic datasets that play a key role in the big data phenomenon that surrounds us today. To extract signals from high-dimensional NGS data and make valid statistical inferences and predictions, novel data analytic and statistical techniques are needed. This book contains 20 chapters written by prominent statisticians working with NGS data. The topics range from basic preprocessing and analysis with NGS data to more complex genomic applications such as copy number variation and isoform expression detection. Research statisticians who want to learn about this growing and exciting area will find this book useful. In addition, many chapters from this book could be included in graduate-level classes in statistical bioinformatics for training future biostatisticians who will be expected to deal with genomic data in basic biomedical research, genomic clinical trials and personalized medicine. About the editors: Somnath Datta is Professor and Vice Chair of Bioinformatics and Biostatistics at the University of Louisville. He is Fellow of the American Statistical Association, Fellow of the Institute of Mathematical Statistics and Elected Member of the International Statistical Institute. He has contributed to numerous research areas in Statistics, Biostatistics and Bioinformatics. Dan Nettleton is Professor and Laurence H. Baker Endowed Chair of Biological Statistics in the Department of Statistics at Iowa State University. He is Fellow of the American Statistical Association and has published research on a variety of topics in statistics, biology and bioinformatics.

Sample Size Calculations in Clinical Research

Author : Shein-Chung Chow
Publisher : CRC Press
ISBN 13 : 1351727117
Total Pages : 825 pages
Book Rating : 4.3/5 (517 download)

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Book Synopsis Sample Size Calculations in Clinical Research by : Shein-Chung Chow

Download or read book Sample Size Calculations in Clinical Research written by Shein-Chung Chow and published by CRC Press. This book was released on 2017-08-15 with total page 825 pages. Available in PDF, EPUB and Kindle. Book excerpt: Praise for the Second Edition: "... this is a useful, comprehensive compendium of almost every possible sample size formula. The strong organization and carefully defined formulae will aid any researcher designing a study." -Biometrics "This impressive book contains formulae for computing sample size in a wide range of settings. One-sample studies and two-sample comparisons for quantitative, binary, and time-to-event outcomes are covered comprehensively, with separate sample size formulae for testing equality, non-inferiority, and equivalence. Many less familiar topics are also covered ..." – Journal of the Royal Statistical Society Sample Size Calculations in Clinical Research, Third Edition presents statistical procedures for performing sample size calculations during various phases of clinical research and development. A comprehensive and unified presentation of statistical concepts and practical applications, this book includes a well-balanced summary of current and emerging clinical issues, regulatory requirements, and recently developed statistical methodologies for sample size calculation. Features: Compares the relative merits and disadvantages of statistical methods for sample size calculations Explains how the formulae and procedures for sample size calculations can be used in a variety of clinical research and development stages Presents real-world examples from several therapeutic areas, including cardiovascular medicine, the central nervous system, anti-infective medicine, oncology, and women’s health Provides sample size calculations for dose response studies, microarray studies, and Bayesian approaches This new edition is updated throughout, includes many new sections, and five new chapters on emerging topics: two stage seamless adaptive designs, cluster randomized trial design, zero-inflated Poisson distribution, clinical trials with extremely low incidence rates, and clinical trial simulation.

The Social Biology of Microbial Communities

Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309264324
Total Pages : 633 pages
Book Rating : 4.3/5 (92 download)

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Book Synopsis The Social Biology of Microbial Communities by : Institute of Medicine

Download or read book The Social Biology of Microbial Communities written by Institute of Medicine and published by National Academies Press. This book was released on 2013-01-10 with total page 633 pages. Available in PDF, EPUB and Kindle. Book excerpt: Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.

Genome Data Analysis

Author : Ju Han Kim
Publisher : Springer
ISBN 13 : 9811319421
Total Pages : 367 pages
Book Rating : 4.8/5 (113 download)

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Book Synopsis Genome Data Analysis by : Ju Han Kim

Download or read book Genome Data Analysis written by Ju Han Kim and published by Springer. This book was released on 2019-04-30 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook describes recent advances in genomics and bioinformatics and provides numerous examples of genome data analysis that illustrate its relevance to real world problems and will improve the reader’s bioinformatics skills. Basic data preprocessing with normalization and filtering, primary pattern analysis, and machine learning algorithms using R and Python are demonstrated for gene-expression microarrays, genotyping microarrays, next-generation sequencing data, epigenomic data, and biological network and semantic analyses. In addition, detailed attention is devoted to integrative genomic data analysis, including multivariate data projection, gene-metabolic pathway mapping, automated biomolecular annotation, text mining of factual and literature databases, and integrated management of biomolecular databases. The textbook is primarily intended for life scientists, medical scientists, statisticians, data processing researchers, engineers, and other beginners in bioinformatics who are experiencing difficulty in approaching the field. However, it will also serve as a simple guideline for experts unfamiliar with the new, developing subfield of genomic analysis within bioinformatics.

Neuroproteomics

Author : Oscar Alzate
Publisher : CRC Press
ISBN 13 : 1420076264
Total Pages : 356 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Neuroproteomics by : Oscar Alzate

Download or read book Neuroproteomics written by Oscar Alzate and published by CRC Press. This book was released on 2009-10-26 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this, the post-genomic age, our knowledge of biological systems continues to expand and progress. As the research becomes more focused, so too does the data. Genomic research progresses to proteomics and brings us to a deeper understanding of the behavior and function of protein clusters. And now proteomics gives way to neuroproteomics as we beg

Nonparametrics

Author : Erich L. Lehmann
Publisher : Springer
ISBN 13 : 9780387563794
Total Pages : 464 pages
Book Rating : 4.5/5 (637 download)

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Book Synopsis Nonparametrics by : Erich L. Lehmann

Download or read book Nonparametrics written by Erich L. Lehmann and published by Springer. This book was released on 2008-11-01 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rank tests are a class of statistical procedures that combine great simplicity with surprising power. This reprint of a classic reference book offers a thorough description of these tests and the estimating procedures derived from them, and gives an account of their properties. Although the field of rank tests has seen little change, important new methodologies have sprung up that also serve the purpose of freeing statistics from the unrealistic model assumptions that so frequently invalidate its applications. All the tests discussed here are now available in a variety of statistical software packages.

The Microbiota in Gastrointestinal Pathophysiology

Author : Martin H. Floch
Publisher : Academic Press
ISBN 13 : 0128040629
Total Pages : 444 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis The Microbiota in Gastrointestinal Pathophysiology by : Martin H. Floch

Download or read book The Microbiota in Gastrointestinal Pathophysiology written by Martin H. Floch and published by Academic Press. This book was released on 2016-11-16 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Microbiota in Gastrointestinal Pathophysiology: Implications for Human Health, Prebiotics, Probiotics and Dysbiosis is a one-stop reference on the state-of-the-art research on gut microbial ecology in relation to human disease. This important resource starts with an overview of the normal microbiota of the gastrointestinal tract, including the esophagus, stomach, Ileum, and colon. The book then identifies what a healthy vs. unhealthy microbial community looks like, including methods of identification. Also included is insight into which features and contributions the microbiota make that are essential and useful to host physiology, as is information on how to promote appropriate mutualisms and prevent undesirable dysbioses. Through the power of synthesizing what is known by experienced researchers in the field, current gaps are closed, raising understanding of the role of the microbiome and allowing for further research. - Explains how to modify the gut microbiota and how the current strategies used to do this produce their effects - Explores the gut microbiota as a therapeutic target - Provides the synthesis of existing data from both mainstream and non-mainstream sources through experienced researchers in the field - Serves as a 'one-stop' shop for a topic that's currently spread across a number of various journals

Modern Multidimensional Scaling

Author : Ingwer Borg
Publisher : Springer Science & Business Media
ISBN 13 : 1475727119
Total Pages : 469 pages
Book Rating : 4.4/5 (757 download)

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Book Synopsis Modern Multidimensional Scaling by : Ingwer Borg

Download or read book Modern Multidimensional Scaling written by Ingwer Borg and published by Springer Science & Business Media. This book was released on 2013-04-18 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multidimensional scaling (MDS) is a technique for the analysis of similarity or dissimilarity data on a set of objects. Such data may be intercorrelations of test items, ratings of similarity on political candidates, or trade indices for a set of countries. MDS attempts to model such data as distances among points in a geometric space. The main reason for doing this is that one wants a graphical display of the structure of the data, one that is much easier to understand than an array of numbers and, moreover, one that displays the essential information in the data, smoothing out noise. There are numerous varieties of MDS. Some facets for distinguishing among them are the particular type of geometry into which one wants to map the data, the mapping function, the algorithms used to find an optimal data representation, the treatment of statistical error in the models, or the possibility to represent not just one but several similarity matrices at the same time. Other facets relate to the different purposes for which MDS has been used, to various ways of looking at or "interpreting" an MDS representation, or to differences in the data required for the particular models. In this book, we give a fairly comprehensive presentation of MDS. For the reader with applied interests only, the first six chapters of Part I should be sufficient. They explain the basic notions of ordinary MDS, with an emphasis on how MDS can be helpful in answering substantive questions.