Design and Analysis of DNA Microarray Investigations

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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.

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About the author (2006)

Dr Richard M. Simon is chief of the Biometric Research Branch of the National Cancer Institute, where he is chief statistician for the Division of Cancer Treatment and Diagnosis. He is the lead author of the textbook Design and Analysis of DNA Microarray Experiments and has more than 450 publications. Simon has been influential in promoting excellence in clinical trial design and analysis. He has served on the Oncologic Advisory Committee of the US Food and Drug Administration and is a frequent advisor to government, academic and industry organizations involved with developing improved treatments and diagnostics for patients with cancer. In 1998 Dr Simon established the Molecular Statistics and Bioinformatics Section of the National Cancer Institute, a multidisciplinary group of scientists developing and applying methods for the application of genomics to cancer therapeutics. He is the architect of BRB-ArrayTools software for the analysis of microarray expression and copy number data.