Eleni M. Tomazou, Daniel J. Turner, Ewan Birney, Paul Flicek, Vardhman K. Rakyan, Kevin L. Howe, David K. Jackson, John C. Marioni, Liselotte Bäckdahl, Simon Tavaré, Marlis Herberth, Heng Li, Marcos Mateo Miretti, Richard Durbin, Javier Herrero, Stephan Beck, Thomas A. Down, Natalie P. Thorne, Stefan Gräf, Nathan Johnson, Eugene Kulesha, and Tim Hubbard
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. © 2008 Nature Publishing Group. Fil: Down, Thomas A.. Wellcome Trust Sanger Institute; Reino Unido Fil: Rakyan, Vardhman K.. Institute of Cell and Molecular Science; Reino Unido Fil: Turner, Daniel J.. Wellcome Trust Sanger Institute; Reino Unido Fil: Flicek, Paul. European Bioinformatics Institute; Reino Unido Fil: Li, Heng. Wellcome Trust Sanger Institute; Reino Unido Fil: Kulesha, Eugene. European Bioinformatics Institute; Reino Unido Fil: Gräf, Stefan. European Bioinformatics Institute; Reino Unido Fil: Johnson, Nathan. European Bioinformatics Institute; Reino Unido Fil: Herrero, Javier. European Bioinformatics Institute; Reino Unido Fil: Tomazou, Eleni M.. Wellcome Trust Sanger Institute; Reino Unido Fil: Thorne, Natalie P.. University of Cambridge; Reino Unido Fil: Bäckdahl, Liselotte. University College London; Reino Unido Fil: Herberth, Marlis. University of Cambridge; Reino Unido Fil: Howe, Kevin L.. University of Cambridge; Reino Unido Fil: Jackson, David K.. Wellcome Trust Sanger Institute; Reino Unido Fil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentina. Wellcome Trust Sanger Institute; Reino Unido Fil: Marioni, John C.. University of Cambridge; Reino Unido Fil: Birney, Ewan. European Bioinformatics Institute; Reino Unido Fil: Hubbard, Tim J. P.. Wellcome Trust Sanger Institute; Reino Unido Fil: Durbin, Richard. Wellcome Trust Sanger Institute; Reino Unido Fil: Tavaré, Simon. University of Cambridge; Reino Unido Fil: Beck, Stephan G.. University College London; Reino Unido