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Briefings in Bioinformatics Advance Access published online on August 9, 2006
Briefings in Bioinformatics, doi:10.1093/bib/bbl023
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© The Author 2006. Published by Oxford University Press. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Papers

Statistically Designing Microarrays and Microarray Experiments to Enhance Sensitivity and Specificity

Jason C. Hsu *, Jane Chang, Tao Wang, Eiríkur Steingrímsson, Magnús Karl Magnússon, and Kristin Bergsteinsdottir

* To whom correspondence should be addressed.
Jason C. Hsu, E-mail: Hsu.1{at}osu.edu


  Abstract

Gene expression signatures from microarray experiments promise to provide important prognostic tools for predicting disease outcome or response to treatment. A number of microarray studies in various cancers have reported such gene signatures. However, the overlap of gene signatures in the same disease has been limited so far, and some reported signatures have not been reproduced in other populations. Clearly, the methods used for verifying novel gene signatures need improvement. In this article, we describe an experiment in which microarrays and sample hybridization are designed according to the statistical principles of randomization, replication and blocking. Our results show that such designs provide unbiased estimation of differential expression levels as well as powerful tests for them.

Keywords: microarray experiments; experimental design; familywise error rate; multiple comparisons; sensitivity and specificity.

Jason Hsu is a Professor in the Department of Statistics at the Ohio State University. He conducts research in multiple comparisons.

Jane Chang is an Assistant Professor of Applied Statistics and Operations Research at Bowling Green State University. Her research interests include optimal experimental design, data analysis and statistical design and analysis of microarray experiments.

Tao Wang is an Assistant Professor of Biostatistics at University of South Florida. His research interests include statistical design and analysis of microarray experiments, bioinformatics and statistical computing.

Eiríkur Steingrímsson is a Professor in the Department of Biochemistry and Molecular Biology in the Faculty of Medicine at the University of Iceland. His research focuses on the role of transcription factors in the development of melanocytes.

Magnús K. Magnússon, MD, is a consulting hematologist and principal investigator in the Departments of Laboratory Hematology and Molecular Medicine & Genetics at Landspitali-University Hospital in Reykjavik. His research interests include leukemogenesis, signaling transduction pathways and gene expression profiling in evaluating disease processes.

Kristin Bergsteinsdottir is a project leader in the Department of Genetics and Molecular Medicine at Landspitali-University Hospital, Reykjavik, Iceland. Her research focus is on gene expression analysis.


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