A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis

By Thomas A. Down, Vardhman K. Rakyan, D. Turner, Paul Flicek, Heng Li, Eugene Kulesha, Stefan Gräf, Nathan Johnson, Javier Herrero, E. Tomazou and 12 more. Nature Biotechnology, 2008

669 citations recorded by the source corpus.

DNA methylation is an indispensible epigenetic modification required for regulating the expression of mammalian genomes. Immunoprecipitation-based methods for DNA methylome analysis are rapidly shifting the bottleneck in this field from data generation to data analysis, necessitating the development of better analytical tools. In particular, an inability to estimate absolute methylation levels remains a major analytical difficulty associated with immunoprecipitation-based DNA methylation profiling. To address this issue, we developed a cross-platform algorithm—Bayesian tool for methylation analysis (Batman)—for analyzing methylated DNA immunoprecipitation (MeDIP) profiles generated using oligonucleotide arrays (MeDIP-chip) or next-generation sequencing (MeDIP-seq). We developed the latter approach to provide a high-resolution whole-genome DNA methylation profile (DNA methylome) of a mammalian genome. Strong correlation of our data, obtained using mature human spermatozoa, with those obtained using bisulfite sequencing suggest that combining MeDIP-seq or MeDIP-chip with Batman provides a robust, quantitative and cost-effective functional genomic strategy for elucidating the function of DNA methylation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e2d8d61a8f665e4d4e39259f22bc20ee18fa4b9b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers (2012, background): “Illumina sequencing has matured to the point where a great many applications [15-24] have been developed on the platform.”
ArrayExpress update—from an archive of functional genomics experiments to the atlas of gene expression (2008, positive): “The ﬁrst sequencing-based data sets to be made public are the transcriptomics landscape for Schizosaccharomyces pombe and epigenomics analysis of human (accession numbers E-MTAB-5 and E-TABM-482) (13,14).”
DNA methylome analysis using short bisulfite sequencing data (2012, methodology): “They range from methylated DNA immunoprecipitation or methyl binding protein enrichment of methylated fragments 18–20 to digestion with methylation-sensitive restriction enzymes 21 and bisulfite modification of DNA 22 .”
An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). (2008, methodology): “Refer to Down et al. (2008) for a detailed description of Batman.”
CpG methylation of half-CRE sequences creates C/EBPα binding sites that activate some tissue-specific genes (2010, background): “These two groups of promoters are similar to those described in a recent study that adjusted the MeDIP enrichment for the CpG density of proximal promoters (27).”