Summary: The minfi package is widely used for analyzing Illumina DNA methylation array data. Here we describe modifications to the minfi package required to support the HumanMethylationEPIC ('EPIC') array from Illumina. We discuss methods for the joint analysis and normalization of data from the HumanMethylation450 ('450k') and EPIC platforms. We introduce the single-sample Noob ( ssNoob ) method, a normalization procedure suitable for incremental preprocessing of individual methylation arrays and conclude that this method should be used when integrating data from multiple generations of Infinium methylation arrays. We show how to use reference 450k datasets to estimate cell type composition of samples on EPIC arrays. The cumulative effect of these updates is to ensure that minfi provides the tools to best integrate existing and forthcoming Illumina methylation array data. Availability and Implementation: The minfi package version 1.19.12 or higher is available for all platforms from the Bioconductor project. Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

MOTIVATION: DNA methylation patterns are well known to vary substantially across cell types or tissues. Hence, existing normalization methods may not be optimal if they do not take this into account. We therefore present a new R package for normalization of data from the Illumina Infinium Human Methylation450 BeadChip (Illumina 450 K) built on the concepts in the recently published funNorm method, and introducing cell-type or tissue-type flexibility. RESULTS: funtooNorm is relevant for data sets containing samples from two or more cell or tissue types. A visual display of cross-validated errors informs the choice of the optimal number of components in the normalization. Benefits of cell (tissue)-specific normalization are demonstrated in three data sets. Improvement can be substantial; it is strikingly better on chromosome X, where methylation patterns have unique inter-tissue variability. AVAILABILITY AND IMPLEMENTATION: An R package is available at https://github.com/GreenwoodLab/funtooNorm, and has been submitted to Bioconductor at http://bioconductor.org.