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Bioinformatics Advance Access originally published online on November 16, 2008
Bioinformatics 2009 25(1):48-53; doi:10.1093/bioinformatics/btn591
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Power enhancement via multivariate outlier testing with gene expression arrays

Adam L. Asare 1,*,{dagger}, Zhong Gao 1,{dagger}, Vincent J. Carey 2,*, Richard Wang 1 and Vicki Seyfert-Margolis 1

1Immune Tolerance Network, University of California – San Francisco, San Francisco, CA 94143 and 2Channing Laboratory, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA 02115, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: As the use of microarrays in human studies continues to increase, stringent quality assurance is necessary to ensure accurate experimental interpretation. We present a formal approach for microarray quality assessment that is based on dimension reduction of established measures of signal and noise components of expression followed by parametric multivariate outlier testing.

Results: We applied our approach to several data resources. First, as a negative control, we found that the Affymetrix and Illumina contributions to MAQC data were free from outliers at a nominal outlier flagging rate of {alpha}=0.01. Second, we created a tunable framework for artificially corrupting intensity data from the Affymetrix Latin Square spike-in experiment to allow investigation of sensitivity and specificity of quality assurance (QA) criteria. Third, we applied the procedure to 507 Affymetrix microarray GeneChips processed with RNA from human peripheral blood samples. We show that exclusion of arrays by this approach substantially increases inferential power, or the ability to detect differential expression, in large clinical studies.

Availability: http://bioconductor.org/packages/2.3/bioc/html/arrayMvout.html and http://bioconductor.org/packages/2.3/bioc/html/affyContam.html affyContam (credentials: readonly/readonly)

Contact: aasare{at}immunetolerance.org; stvjc{at}channing.harvard.edu

{dagger}The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

Associate Editor: Trey Ideker

Received on May 13, 2008; revised on October 10, 2008; accepted on November 11, 2008

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