Modeling dose-response microarray data in early drug development experiments using R

Author(s)

    • Dan, Lin
    • Shkedy, Ziv
    • Yekutieli, Daniel
    • Amaratunga, Dhammika
    • Bijnens, Luc

Bibliographic Information

Modeling dose-response microarray data in early drug development experiments using R

Dan Lin, Ziv Shkedy, Daniel Yekutieli, Dhammika Amaratunga, Luc Bijnens

(Use R! / series editors, Robert Gentleman, Kurt Hornik, Giovanni Parmigiani)

Springer, c2012

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Includes index

Description and Table of Contents

Description

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.

Table of Contents

Introduction.- Part I: Dose-response Modeling: An Introduction.- Estimation Under Order Restrictions.- The Likelihood Ratio Test.- Part II: Dose-response Microarray Experiments.- Functional Genomic Dose-response Experiments.- Adjustment for Multiplicity.- Test for Trend.- Order Restricted Bisclusters.- Classification of Trends in Dose-response Microarray Experiments Using Information Theory Selection Methods.- Multiple Contrast Test.- Confidence Intervals for the Selected Parameters.- Case Study Using GUI in R: Gene Expression Analysis After Acute Treatment With Antipsychotics.

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