This book focuses on the analysis of dose-response microarray data in pharmaceutical settings, the goal being to cover this important topic for early drug development experiments and to provide user-friendly R packages that can be used to analyze this data. It is intended for biostatisticians and bioinformaticians in the pharmaceutical industry, biologists, and biostatistics/bioinformatics graduate students. Part I of the book is an introduction, in which we discuss the dose-response setting and the problem of estimating normal means under order restrictions. In particular, we discuss the pooled-adjacent-violator (PAV) algorithm and isotonic regression, as well as inference under order restrictions and non-linear parametric models, which are used in the second part of the book. Part II is the core of the book, in which we focus on the analysis of dose-response microarray data. Methodological topics discussed include: • Multiplicity adjustment • Test statistics and procedures for the analysis of dose-response microarray data • Resampling-based inference and use of the SAM method for small-variance genes in the data • Identification and classification of dose-response curve shapes • Clustering of order-restricted (but not necessarily monotone) dose-response profiles • Gene set analysis to facilitate the interpretation of microarray results • Hierarchical Bayesian models and Bayesian variable selection • Non-linear models for dose-response microarray data • Multiple contrast tests • Multiple confidence intervals for selected parameters adjusted for the false coverage-statement rate All methodological issues in the book are illustrated using real-world examples of dose-response microarray datasets from early drug development experiments.

Nowadays the term dose-response is used in many different contexts and many different scientific disciplines including agriculture, biochemistry, chemistry, environmental sciences, genetics, pharmacology, plant sciences, toxicology, and zoology. In the 1940 and 1950s, dose-response analysis was intimately linked to evaluation of toxicity in terms of binary responses, such as immobility and mortality, with a limited number of doses of a toxic compound being compared to a control group (dose 0). Later, dose-response analysis has been extended to other types of data and to more complex experimental designs. Moreover, estimation of model parameters has undergone a dramatic change, from struggling with cumbersome manual operations and transformations with pen and paper to rapid calculations on any laptop. Advances in statistical software have fueled this development. Key Features: Provides a practical and comprehensive overview of dose-response analysis. Includes numerous real data examples to illustrate the methodology. R code is integrated into the text to give guidance on applying the methods. Written with minimal mathematics to be suitable for practitioners. Includes code and datasets on the book’s GitHub: https://github.com/DoseResponse. This book focuses on estimation and interpretation of entirely parametric nonlinear dose-response models using the powerful statistical environment R. Specifically, this book introduces dose-response analysis of continuous, binomial, count, multinomial, and event-time dose-response data. The statistical models used are partly special cases, partly extensions of nonlinear regression models, generalized linear and nonlinear regression models, and nonlinear mixed-effects models (for hierarchical dose-response data). Both simple and complex dose-response experiments will be analyzed.

The apparent contradiction between statistical significance and biological relevance has diminished the value of statistical methods as a whole in toxicology. Moreover, recommendations for statistical analysis are imprecise in most toxicological guidelines. Addressing these dilemmas, Statistics in Toxicology Using R explains the statistical analysi

Praise for the First Edition “...extremely well written...a comprehensive and up-to-date overview of this important field.” – Journal of Environmental Quality Exploration and Analysis of DNA Microarray and Other High-Dimensional Data, Second Edition provides comprehensive coverage of recent advancements in microarray data analysis. A cutting-edge guide, the Second Edition demonstrates various methodologies for analyzing data in biomedical research and offers an overview of the modern techniques used in microarray technology to study patterns of gene activity. The new edition answers the need for an efficient outline of all phases of this revolutionary analytical technique, from preprocessing to the analysis stage. Utilizing research and experience from highly-qualified authors in fields of data analysis, Exploration and Analysis of DNA Microarray and Other High-Dimensional Data, Second Edition features: A new chapter on the interpretation of findings that includes a discussion of signatures and material on gene set analysis, including network analysis New topics of coverage including ABC clustering, biclustering, partial least squares, penalized methods, ensemble methods, and enriched ensemble methods Updated exercises to deepen knowledge of the presented material and provide readers with resources for further study The book is an ideal reference for scientists in biomedical and genomics research fields who analyze DNA microarrays and protein array data, as well as statisticians and bioinformatics practitioners. Exploration and Analysis of DNA Microarray and Other High-Dimensional Data, Second Edition is also a useful text for graduate-level courses on statistics, computational biology, and bioinformatics.

Proven Methods for Big Data Analysis As big data has become standard in many application areas, challenges have arisen related to methodology and software development, including how to discover meaningful patterns in the vast amounts of data. Addressing these problems, Applied Biclustering Methods for Big and High-Dimensional Data Using R shows how to apply biclustering methods to find local patterns in a big data matrix. The book presents an overview of data analysis using biclustering methods from a practical point of view. Real case studies in drug discovery, genetics, marketing research, biology, toxicity, and sports illustrate the use of several biclustering methods. References to technical details of the methods are provided for readers who wish to investigate the full theoretical background. All the methods are accompanied with R examples that show how to conduct the analyses. The examples, software, and other materials are available on a supplementary website.

Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics near the end and in the appendices. A background in basic linear regression and categorical data analysis, as well as a basic knowledge of calculus and the R system, will help the reader to fully appreciate the information presented. Examples are simple and straightforward while still illustrating key points, shedding light on the application of survival analysis in a way that is useful for graduate students, researchers, and practitioners in biostatistics.