NDLI: Using control genes to correct for unwanted variation in microarray data

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Using control genes to correct for unwanted variation in microarray data

Content Provider	PubMed Central
Author	Gagnon-bartsch, Johann A. Speed, Terence P.
Copyright Year	2011
Abstract	Microarray expression studies suffer from the problem of batch effects and other unwanted variation. Many methods have been proposed to adjust microarray data to mitigate the problems of unwanted variation. Several of these methods rely on factor analysis to infer the unwanted variation from the data. A central problem with this approach is the difficulty in discerning the unwanted variation from the biological variation that is of interest to the researcher. We present a new method, intended for use in differential expression studies, that attempts to overcome this problem by restricting the factor analysis to negative control genes. Negative control genes are genes known a priori not to be differentially expressed with respect to the biological factor of interest. Variation in the expression levels of these genes can therefore be assumed to be unwanted variation. We name this method “Remove Unwanted Variation, 2-step” (RUV-2). We discuss various techniques for assessing the performance of an adjustment method and compare the performance of RUV-2 with that of other commonly used adjustment methods such as Combat and Surrogate Variable Analysis (SVA). We present several example studies, each concerning genes differentially expressed with respect to gender in the brain and find that RUV-2 performs as well or better than other methods. Finally, we discuss the possibility of adapting RUV-2 for use in studies not concerned with differential expression and conclude that there may be promise but substantial challenges remain.
Related Links	http://dx.doi.org/10.1093/biostatistics/kxr034
Ending Page	552
Page Count	14
Starting Page	539
File Format	PDF
ISSN	14654644
e-ISSN	14684357
Journal	Biostatistics (Oxford, England)
Issue Number	3
Volume Number	13
Language	English
Publisher	Oxford University Press
Publisher Date	2012-07-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Statistics, Probability and Uncertainty Statistics and Probability Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Statistics and Probability Medicine Statistics, Probability and Uncertainty

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