RT Journal Article SR Electronic T1 Functional normalization of 450k methylation array data improves replication in large cancer studies JF bioRxiv FD Cold Spring Harbor Laboratory SP 002956 DO 10.1101/002956 A1 Jean-Philippe Fortin A1 Aurélie Labbe A1 Mathieu Lemire A1 Brent W. Zanke A1 Thomas J. Hudson A1 Elana J. Fertig A1 Celia M.T. Greenwood A1 Kasper D. Hansen YR 2014 UL http://biorxiv.org/content/early/2014/02/23/002956.abstract AB We propose an extension to quantile normalization which removes unwanted technical variation using control probes. We adapt our algorithm, functional normalization, to the Illumina 450k methylation array and address the open problem of normalizing methylation data with global epigenetic changes, such as human cancers. Using datasets from The Cancer Genome Atlas and a large case-control study, we show that our algorithm outperforms all existing normalization methods with respect to replication of results between experiments, and yields robust results even in the presence of batch effects. Functional normalization can be applied to any microarray platform, provided suitable control probes are available.