metilene: fast and sensitive calling of differentially methylated regions from bisulfite sequencing data

• Published in: Genome research Vol. 26; no. 2; pp. 256 - 262
• Main Authors: Jühling, Frank, Kretzmer, Helene, Bernhart, Stephan H., Otto, Christian, Stadler, Peter F., Hoffmann, Steve
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.02.2016
• Subjects: Algorithms; Biochemistry, Molecular Biology; Case-Control Studies; Cerebellar Neoplasms - genetics; CpG Islands; DNA Methylation; Genomics; Humans; Life Sciences; Medulloblastoma - genetics; Method; Quantitative Methods; Sequence Analysis, DNA; Software
• ISSN: 1088-9051; 1549-5469; 1549-5469
• DOI: 10.1101/gr.196394.115

The detection of differentially methylated regions (DMRs) is a necessary prerequisite for characterizing different epigenetic states. We present a novel program, metilene, to identify DMRs within whole-genome and targeted data with unrivaled specificity and sensitivity. A binary segmentation algorithm combined with a two-dimensional statistical test allows the detection of DMRs in large methylation experiments with multiple groups of samples in minutes rather than days using off-the-shelf hardware. metilene outperforms other state-of-the-art tools for low coverage data and can estimate missing data. Hence, metilene is a versatile tool to study the effect of epigenetic modifications in differentiation/development, tumorigenesis, and systems biology on a global, genome-wide level. Whether in the framework of international consortia with dozens of samples per group, or even without biological replicates, it produces highly significant and reliable results.