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

Order-Restricted Analysis of Microarray Data

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

Part of the Use R! book series (USE R)

Table of contents

  1. Front Matter
    Pages i-xv
  2. Dose-response Modeling: An Introduction

    1. Front Matter
      Pages 9-9
    2. Dan Lin, Willem Talloen, Luc Bijnens, Hinrich W. H. Göhlmann, Dhammika Amaratunga, Roel Straetemans
      Pages 1-7
    3. Ziv Shkedy, Dhammika Amaratunga, Marc Aerts
      Pages 11-27
    4. Ziv Shkedy, Dhammika Amaratunga, Dan Lin
      Pages 29-42
    5. Roel Straetemans
      Pages 43-66
  3. Dose-response Microarray Experiments

    1. Front Matter
      Pages 67-67
    2. Luc Bijnens, Hinrich W. H. Göhlmann, Dan Lin, Willem Talloen, Tim Perrera, Ilse Van Den Wyngaert et al.
      Pages 69-80
    3. Daniel Yekutieli, Dan Lin, Ziv Shkedy, Dhammika Amaratunga
      Pages 81-101
    4. Dan Lin, Ziv Shkedy, Daniel Yekutieli, Tomasz Burzykowski, Hinrich W. H. Göhlmann, An De Bondt et al.
      Pages 103-121
    5. Dan Lin, Ziv Shkedy, Hinrich W. H. Göhlmann, An De Bondt, Luc Bijnens, Dhammika Amaratunga et al.
      Pages 123-133
    6. Adetayo Kasim, Suzy Van Sanden, Martin Otava, Sepp Hochreiter, Djork-Arné Clevert, Willem Talloen et al.
      Pages 135-149
    7. Dan Lin, Ziv Shkedy
      Pages 165-180
    8. Nandini Raghavan, An De Bondt, Tobias Verbeke, Dhammika Amaratunga
      Pages 181-191
    9. Setia Pramana, Ziv Shkedy, Hinrich W. H. Göhlmann, Willem Talloen, An De Bondt, Roel Straetemans et al.
      Pages 215-232
    10. Dan Lin, Ludwig A. Hothorn, Gemechis D. Djira, Frank Bretz
      Pages 233-247
    11. Dan Lin, Gemechis D. Djira, Ziv Shkedy, Tomasz Burzykowski, Ludwig A. Hothorn
      Pages 249-258
    12. Dan Lin, Daniel Yekutieli, Gemechis D. Djira, Ludwig A. Hothorn
      Pages 259-267
    13. Setia Pramana, Philippe Haldermans, Tobias Verbeke
      Pages 269-279
  4. Back Matter
    Pages 281-282

About this book


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.


Dose-response microarray data Estimation and inference under order restrictions Gene expression R

Editors and affiliations

  • Dan Lin
    • 1
  • Ziv Shkedy
    • 2
  • Daniel Yekutieli
    • 3
  • Dhammika Amaratunga
    • 4
  • Luc Bijnens
    • 5
  1. 1., VMRDPfizer Animal HealthZaventemBelgium
  2. 2.Center for StatisticsHasselt UniversityDiepenbeekBelgium
  3. 3., Department of Statistics andSchool of Mathematical SciencesTel AvivIsrael
  4. 4.Johnson & JohnsonRaritanUSA
  5. 5., Biostatistics and Programming Center ofJanssen PharmaceuticaBeerseBelgium

Bibliographic information