Modeling Dose-Response Microarray Data in Early Drug Development Using R
The IsoGene Project
The IsoGene Project is a project aimed for developing methodology and software to perform analysis of dose-response microarray studies. Bioinformatics and Statistical bioinformatics are multidisciplinary areas. The materials for the ISoGene project were developed over the last 7 years by a group of biologists, biostatisticians, mathematical statisticians, computer scientists from both academia and pharmaceutical industry. Most of the collaborators are part of the CHIPS-network (Common Hour Involving Practical Statistics). This network was initiated about ten years ago as two weekly workshops to give statisticians, bio-informaticists and life scientists the opportunity to integrate expertise on the design and analysis microarray experiments. The network has a strong culture of sharing knowledge and expertise between the different professions.
The methodology and software implementation developed in the project are described in the book "Modeling dose-response microarray data in early drug development using R". The book covers the following topics:
Estimation and inference under order constrains.
Parametric modeling of dose-response microarray data.
Permutation test and resampling based inference and multiple testing.
Significance analysis if dose-response microarray data (SAM)
Order restricted clustering.
Classification genes based on information criteria.
Hierarchical Bayesian approach.
Model based approach for dose-response microarray data.
Gene set analysis.
Multiple contrast tests.
FDR adjusted confidence intervals for selected parameters
For the R code of the analysis presented in the book chapters click here.
Three packages in R were developed in this project:
The IsoGene package is a command based package inR in which all the methodology is implemented.
The Graphical User Interface (IsoGeneGUI) is a user friendly interface of the IsoGene package which is developed for the user with no or limited knowledge about R. The IsoGeneGUI was developed using tcl/tk.
The R package ORCM is a command based package for order restricted clustering of dose-response microarray data.
In addition to IsoGene and IsoGeneGUI various R packages are applied for specific settings, which include nlme, multtest, ORCM, MLP, BRUGs, MCPMod, DoseFinding, multcomp and mratios. The working assumption is that the users have a basic knowledge of R and therefore complete working examples are provided for the data analyzes presented in the book. Readers with very limited knowledge of R that wish to perform the analyzes presented in the book can do it easily using the IsoGeneGUI which does not require knowledge in R syntax.
Marc Aerts, Dhammika Amaratunga , Luc Bijnens Frank Bretz, Tomasz Burzykowski, Djork-Arné Clevet, An De Bondt, Gemechis D. Dijra, Filip De Ridder, Göhlmann, Philippe Haldermans, Sepp Hochreiter, Ludwig Hothorn, Adetayo Kasim, Bernet Kato, Martin Otava, Setia Pramana, Pieter Peeters, Tim Perrera, Jose Pinheiro, Nandini Raghavan, Ziv Shkedy Roel Straetemans, Willem Talloen, Suzy Van Sanden, Tobias Verbeke and Dani Yekutieli.
Software developers (IsoGene, IsoGeneGUI and ORCME)
Dan Lin, Setia Pramana, Martin Otava,Tobias Verbeke, Philippe Haldermans.