Between-array normalization for 450K data

The Illumina Infinium HumanMethylation450 BeadChip is frequently used in epigenetic research. Besides quantile normalization there is currently no standard method to normalize the data between arrays. We describe some properties of the data generated by this platform and present a normalization method based on local regression. We compare the performance of this method with other commonly used approaches in three benchmarks (correlation between 21 pairs of technical replicates, detection of differential methylation and correlation of methylation levels for smoking-associated CpG sites with smoking behavior of 655 participants of an epidemiological study). Results indicate that the proposed method improves reproducibility, whereas some commonly used methods can have adverse effects.