Effect of Normalization on Significance Testing for Oligonucleotide Microarrays

Abstract
Motivation. Normalization techniques are used to reduce variation among gene expression measurements in oligonucleotide microarrays in an effort to improve the quality of the data and the power of significance tests for detecting differential expression. Of several such proposed methods, two that have commonly been employed include median–interquartile range normalization and quantile normalization. The median–IQR method applied directly to fold-changes for paired data also was considered. Two methods for calculating gene expression values include the MAS 5.0 algorithm [Affymetrix. (2002). Statistical Algorithms Description Document. Santa Clara, CA: Affymetrix, Inc. http://www.affymetrix.com/support/technical/whitepapers/sadd-whitepaper. pdf] and the RMA method [Irizarry, R. A., Bolstad, B. M., Collin, F., Cope, L. M., Hobbs, B., Speed, T. P. (2003a). Summaries of Affymetrix Gene- Chip probe level data. Nucleic Acids Res. 31(4,e15); Irizarry, R. A., Hobbs, B., Collin, F., Beazer-Barclay, Y. D., ...