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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.

SUBMITTER: Fortin JP 

PROVIDER: S-EPMC4283580 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Functional normalization of 450k methylation array data improves replication in large cancer studies.

Fortin Jean-Philippe JP   Labbe Aurélie A   Lemire Mathieu M   Zanke Brent W BW   Hudson Thomas J TJ   Fertig Elana J EJ   Greenwood Celia Mt CM   Hansen Kasper D KD  

Genome biology 20141203 12


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  ...[more]

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