ADMIRE: Analysis and visualization of differential methylation in genomic regions using the Infinium HumanMethylation450 Assay

Abstract

Background: DNA methylation at cytosine nucleotides constitutes epigenetic gene regulation impacting cellular development and a wide range of diseases. Cytosine bases of the DNA are converted to 5-methylcytosine by the methyltransferase enzyme, acting as a reversible regulator of gene expression. Due to its outstanding importance in the epigenetic field, a number of lab techniques were developed to interrogate DNA methylation on a global range. Besides whole-genome bisulfite sequencing, the Infinium HumanMethylation450 Assay represents a versatile and cost-effective tool to investigate genome-wide changes of methylation patterns. Results: Analysis of DNA Methylation In genomic REgions (ADMIRE) is an open source, semi-automatic analysis pipeline and visualization tool for Infinium HumanMethylation450 Assays with a special focus on ease of use. It features flexible experimental settings, quality control, automatic filtering, normalization, multiple testing, and differential analyses on arbitrary genomic regions. Publication-ready graphics, genome browser tracks, and table outputs include summary data and statistics, permitting instant comparison of methylation profiles between sample groups and the exploration of methylation patterns along the whole genome. ADMIREs statistical approach permits simultaneous large-scale analyses of hundreds of assays with little impact on algorithm runtimes. Conclusions: The web-based version of ADMIRE provides a simple interface to researchers with limited programming skills, whereas the offline version is suitable for integration into custom pipelines. ADMIRE may be used via our freely available web service at https://bioinformatics.mpi-bn.mpg.de without any limitations concerning the size of a project. An offline version for local execution is available from our website or GitHub (https://github.molgen.mpg.de/loosolab/admire).