Modeling Dose-Response Microarray Data in Early Drug Development Experiments Using R

This book focuses on the analysis of dose-response microarray data in pharmaceutical setting, the goal being to cover this important topic for early drug development and to provide user-friendly R packages that can be used to analyze dose-response microarray 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 the likelihood ratio test and non-linear parametric models, which are used in the second part of the book. §Part II is the core of the book. Methodological topics discussed include:§· Multiplicity adjustment§· Test statistics and testing procedures for the analysis of dose-response microarray data§· Resampling-based inference and use of the SAM method at the presence of 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§· Hierarchical Bayesian models and non-linear models for dose-response microarray data§· Multiple contrast tests§All methodological issues in the book are illustrated using four real-world examples of dose-response microarray datasets from early drug development experiments.This book focuses on the analysis of dose-response microarray data in pharmaceutical setting, the goal being to cover this important topic for early drug development and to provide user-friendly R packages that can be used to analyze dose-response microarray 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 the likelihood ratio test and non-linear parametric models, which are used in the second part of the book. §Part II is the core of the book. Methodological topics discussed include:§· Multiplicity adjustment§· Test statistics and testing procedures for the analysis of dose-response microarray data §· Resampling-based inference and use of the SAM method at the presence of 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§· Hierarchical Bayesian models and non-linear models for dose-response microarray data§· Multiple contrast tests§All methodological issues in the book are illustrated using four real-world examples of dose-response microarray datasets from early drug development experiments.