Bioinformatics Advance Access originally published online on July 5, 2005
Bioinformatics 2005 21(17):3530-3534; doi:10.1093/bioinformatics/bti570
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Increased power of microarray analysis by use of an algorithm based on a multivariate procedure
1Interdisciplinary Center for Clinical Research Leipzig, University of Leipzig Inselstrasse 22, 04103 Leipzig, Germany
2III. Medical Department, University of Leipzig Ph.-Rosenthal-Strasse 27, 04103 Leipzig, Germany
3Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig Haertelstrasse 16-18,04107 Leipzig, Germany
*To whom correspondence should be addressed.
Motivation: The power of microarray analyses to detect differential gene expression strongly depends on the statistical and bioinformatical approaches used for data analysis. Moreover, the simultaneous testing of tens of thousands of genes for differential expression raises the ‘multiple testing problem’, increasing the probability of obtaining false positive test results. To achieve more reliable results, it is, therefore, necessary to apply adjustment procedures to restrict the family-wise type I error rate (FWE) or the false discovery rate. However, for the biologist the statistical power of such procedures often remains abstract, unless validated by an alternative experimental approach.
Results: In the present study, we discuss a multiplicity adjustment procedure applied to classical univariate as well as to recently proposed multivariate gene-expression scores. All procedures strictly control the FWE. We demonstrate that the use of multivariate scores leads to a more efficient identification of differentially expressed genes than the widely used MAS5 approach provided by the Affymetrix software tools (Affymetrix Microarray Suite 5 or GeneChip Operating Software). The practical importance of this finding is successfully validated using real time quantitative PCR and data from spike-in experiments.
Availability: The R-code of the statistical routines can be obtained from the corresponding author.
Contact: Schuster{at}imise.uni-leipzig.de
Received on February 11, 2005; revised on July 1, 2005; accepted on July 1, 2005
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