{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:21:36Z","timestamp":1764688896441},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Methylation of cytosines in DNA is an important epigenetic mechanism involved in transcriptional regulation and preservation of genome integrity in a wide range of eukaryotes. Immunoprecipitation of methylated DNA followed by hybridization to genomic tiling arrays (MeDIP-chip) is a cost-effective and sensitive method for methylome analyses. However, existing bioinformatics methods only enable a binary classification into unmethylated and methylated genomic regions, which limit biological interpretations. Indeed, DNA methylation levels can vary substantially within a given DNA fragment depending on the number and degree of methylated cytosines. Therefore, a method for the identification of more than two methylation states is highly desirable.<\/jats:p><jats:p>Results: Here, we present a three-state hidden Markov model (MeDIP-HMM) for analyzing MeDIP-chip data. MeDIP-HMM uses a higher-order state-transition process improving modeling of spatial dependencies between chromosomal regions, allows a simultaneous analysis of replicates and enables a differentiation between unmethylated, methylated and highly methylated genomic regions. We train MeDIP-HMM using a Bayesian Baum\u2013Welch algorithm, integrating prior knowledge on methylation levels. We apply MeDIP-HMM to the analysis of the Arabidopsis root methylome and systematically investigate the benefit of using higher-order HMMs. Moreover, we also perform an in-depth comparison study with existing methods and demonstrate the value of using MeDIP-HMM by comparisons to current knowledge on the Arabidopsis methylome. We find that MeDIP-HMM is a fast and precise method for the analysis of methylome data, enabling the identification of distinct DNA methylation levels. Finally, we provide evidence for the general applicability of MeDIP-HMM by analyzing promoter DNA methylation data obtained for chicken.<\/jats:p><jats:p>Availability: MeDIP-HMM is available as part of the open-source Java library Jstacs (www.jstacs.de\/index.php\/MeDIP-HMM). Data files are available from the Jstacs website.<\/jats:p><jats:p>Contact: \u00a0seifert@ipk-gatersleben.de<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts562","type":"journal-article","created":{"date-parts":[[2012,9,19]],"date-time":"2012-09-19T00:59:41Z","timestamp":1348016381000},"page":"2930-2939","source":"Crossref","is-referenced-by-count":24,"title":["MeDIP-HMM: genome-wide identification of distinct DNA methylation states from high-density tiling arrays"],"prefix":"10.1093","volume":"28","author":[{"given":"Michael","family":"Seifert","sequence":"first","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"},{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"},{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Cortijo","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Colom\u00e9-Tatch\u00e9","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Johannes","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Roudier","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Colot","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany, 2Institut de Biologie de l\u2019Ecole Normale Sup\u00e9rieure, Centre National de la Recherche Scientifique (CNRS), UMR8197, Paris, France, 3Cellular Networks and Systems Biology, Biotechnology Center of the Technical University Dresden, Dresden, Germany and 4Groningen Bioinformatics Centre, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,9,17]]},"reference":[{"key":"2023012513234429500_bts562-B1","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1093\/nar\/gkr324","article-title":"Genome-wide evidence for local DNA methylation spreading from small RNA-targeted sequences in Arabidopsis","volume":"39","author":"Ahmed","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023012513234429500_bts562-B2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1365-313X.2011.04628.x","article-title":"Additive inheritance of histone modifications in Arabidopsis thaliana intraspecific hybrids","volume":"67","author":"Banaei","year":"2011","journal-title":"Plant 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