Design and Analysis of DNA Microarray Investigations

DNA microarrays are an important technology for studying gene expression. With a single hybridization, the level of expression of thousands of genes, or even an entire genome, can be estimated for a sample of cells. Consequently, manylaboratoriesareattemptingtoutilizeDNAmicroarraysintheirresearch. Whereaslaboratoriesarewellpreparedtoaddressthesigni?cantexperimental challenges in obtaining reproducible data from this RNA-based assay, inv- tigators are less prepared to analyze the large volumes of data produced by DNA microarrays. Although many software packages have been developed for the analysis of DNA microarray data, software alone is insu?cient. One needs knowledge aboutthevariousaspectsofdataanalysisinordertoselectandutilizesoftware e?ectively. There is a plethora of analysis methods being published and it is di?cult for biologists to determine which methods are valid and appropriate for their problems. Many scientists have learned that software is not an adequate substitute for biostatistical knowledge and seek statistical collaborators. Unfortunately, there is presently a shortage of statisticians who are available and knowled- able about DNA microarrays. For statisticians to be e?ective collaborators in anyarea,theymustinvestthetimetounderstandthesubjectmatterareaand become familiar with the literature so that they can ask the right questions and identify the key issues. Our objectives in this book are twofold: to provide scientists with infor- tion about the design and analysis of studies using DNA microarrays that will enable them to plan and analyze their own studies or to work with statistical collaborators e?ectively, and to aid statistical and computational scientists wishing to develop expertise in this area.

This book is targeted to biologists with limited statistical background and to statisticians and computer scientists interested in being effective collaborators on multi-disciplinary DNA microarray projects. State-of-the-art analysis methods are presented with minimal mathematical notation and a focus on concepts. This book is unique because it is authored by statisticians at the National Cancer Institute who are actively involved in the application of microarray technology.

Many laboratories are not equipped to effectively design and analyze studies that take advantage of the promise of microarrays. Many of the software packages available to biologists were developed without involvement of statisticians experienced in such studies and contain tools that may not be optimal for particular applications. This book provides a sound preparation for designing microarray studies that have clear objectives, and for selecting analysis tools and strategies that provide clear and valid answers. The book offers an in depth understanding of the design and analysis of experiments utilizing microarrays and should benefit scientists regardless of what software packages they prefer. In order to provide all readers with hands on experience in data analysis, it includes an Appendix tutorial on the use of BRB-ArrayTools and step by step analyses of several major datasets using this software which is freely available from the National Cancer Institute for non-commercial use.

The authors are current or former members of the Biometric Research Branch at the National Cancer Institute.  They have collaborated on major biomedical studies utilizing microarrays and in the development of statistical methodology for the design and analysis of microarray investigations. Dr. Simon, chief of the branch, is also the architect of BRB-ArrayTools.