@article{f397f4b0c66245b29c226d23a37cc245,
title = "Functional normalization of 450k methylation array data improves replication in large cancer studies",
abstract = "We propose an extension to quantile normalization that 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 data sets 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.",
author = "Fortin, {Jean Philippe} and Aur{\'e}lie Labbe and Mathieu Lemire and Zanke, {Brent W.} and Hudson, {Thomas J.} and Fertig, {Elana J.} and Greenwood, {Celia M.T.} and Hansen, {Kasper D.}",
note = "Funding Information: Funding for the methylation genotyping was obtained from a GL2 grant from the Ontario Research Fund to BWZ and TJH. The Colon Cancer Family Registry is supported by the National Cancer Institute, National Institutes of Health under RFA CA-95-011. The Ontario Familial Colon Cancer Registry is supported by grant U01 CA074783. JPF and AL were partially supported by les Fonds de Recherche en Sant{\'e} du Qu{\'e}bec, the Natural Sciences and Engineering Research Council of Canada and les Fonds de recherche Nature et technologies du Qu{\'e}bec. A pilot project from the Johns Hopkins Head and Neck Cancer SPORE supported EJF. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM083084. TJH and BWZ are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. EJF is also supported by the National Cancer Institute (CA141053). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Colon Cancer Registries, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the Colon Cancer Registries. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2014 Fortin et al.",
year = "2014",
month = dec,
day = "3",
doi = "10.1186/s13059-014-0503-2",
language = "English (US)",
volume = "15",
journal = "Genome Biology",
issn = "1474-7596",
publisher = "BioMed Central",
number = "11",
}