{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T22:16:45Z","timestamp":1774649805528,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":583,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Genome-wide mapping of chromatin states is essential for defining regulatory elements and inferring their activities in eukaryotic genomes. A number of hidden Markov model (HMM)-based methods have been developed to infer chromatin state maps from genome-wide histone modification data for an individual genome. To perform a principled comparison of evolutionarily distant epigenomes, we must consider species-specific biases such as differences in genome size, strength of signal enrichment and co-occurrence patterns of histone modifications.<\/jats:p><jats:p>Results: Here, we present a new Bayesian non-parametric method called hierarchically linked infinite HMM (hiHMM) to jointly infer chromatin state maps in multiple genomes (different species, cell types and developmental stages) using genome-wide histone modification data. This flexible framework provides a new way to learn a consistent definition of chromatin states across multiple genomes, thus facilitating a direct comparison among them. We demonstrate the utility of this method using synthetic data as well as multiple modENCODE ChIP-seq datasets.<\/jats:p><jats:p>Conclusion: The hierarchical and Bayesian non-parametric formulation in our approach is an important extension to the current set of methodologies for comparative chromatin landscape analysis.<\/jats:p><jats:p>Availability and implementation: Source codes are available at https:\/\/github.com\/kasohn\/hiHMM. Chromatin data are available at http:\/\/encode-x.med.harvard.edu\/data_sets\/chromatin\/.<\/jats:p><jats:p>Contact: \u00a0peter_park@harvard.edu or juhan@snu.ac.kr<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv117","type":"journal-article","created":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T01:22:16Z","timestamp":1425172936000},"page":"2066-2074","source":"Crossref","is-referenced-by-count":49,"title":["hiHMM: Bayesian non-parametric joint inference of chromatin state maps"],"prefix":"10.1093","volume":"31","author":[{"given":"Kyung-Ah","family":"Sohn","sequence":"first","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua W. K.","family":"Ho","sequence":"additional","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djordje","family":"Djordjevic","sequence":"additional","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-hwan","family":"Jeong","sequence":"additional","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Park","sequence":"additional","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Han","family":"Kim","sequence":"additional","affiliation":[{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Department of Information and Computer Engineering, Ajou University, Suwon 443-749, South Korea, 2Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea, 3Systems Biomedical Informatics Research Center, Seoul National University, Seoul 110799, Korea, 4Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia, 5The University of New South Wales, Sydney, NSW 2052, Australia, 6Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA and 7Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,2,27]]},"reference":[{"key":"2023020202145602000_btv117-B1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nmeth.1673","article-title":"Making sense of chromatin states","volume":"8","author":"Baker","year":"2011","journal-title":"Nat. Methods"},{"key":"2023020202145602000_btv117-B2","first-page":"577","article-title":"The infinite hidden Markov model","volume":"Vol. 14","author":"Beal","year":"2002","journal-title":"Advances in Neural Information Processing Systems"},{"key":"2023020202145602000_btv117-B3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. B"},{"key":"2023020202145602000_btv117-B4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2006.02.041","article-title":"A bivalent chromatin structure marks key developmental genes in embryonic stem cells","volume":"125","author":"Bernstein","year":"2006","journal-title":"Cell"},{"key":"2023020202145602000_btv117-B5","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1471-2105-14-S5-S4","article-title":"Discovering and mapping chromatin states using a tree hidden Markov model","volume":"14","author":"Biesinger","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023020202145602000_btv117-B6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1214\/aos\/1176342372","article-title":"Ferguson distributions via polya urn schemes","volume":"1","author":"Blackwell","year":"1973","journal-title":"Ann. Stat."},{"key":"2023020202145602000_btv117-B7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"ENCODE Project Consortium","year":"2012","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B8","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nbt.1662","article-title":"Discovery and characterization of chromatin states for systematic annotation of the human genome","volume":"28","author":"Ernst","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2023020202145602000_btv117-B9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nmeth.1906","article-title":"ChromHMM: automating chromatin-state discovery and characterization","volume":"9","author":"Ernst","year":"2012","journal-title":"Nat. Methods"},{"key":"2023020202145602000_btv117-B10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature09906","article-title":"Mapping and analysis of chromatin state dynamics in nine human cell types","volume":"473","author":"Ernst","year":"2011","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1214\/aos\/1176342360","article-title":"A Bayesian analysis of some nonparametric problems","volume":"1","author":"Ferguson","year":"1973","journal-title":"Ann. Stat."},{"key":"2023020202145602000_btv117-B12","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.cell.2010.09.009","article-title":"Systematic protein location mapping reveals five principal chromatin types in drosophila cells","volume":"143","author":"Filion","year":"2010","journal-title":"Cell"},{"key":"2023020202145602000_btv117-B13","first-page":"268","article-title":"The viterbi algorithm","volume-title":"Proceedings of the IEEE, Vol. 61, IEEE, .","author":"Forney","year":"1973"},{"key":"2023020202145602000_btv117-B14","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature07829","article-title":"Histone modifications at human enhancers reflect global cell-type-specific gene expression","volume":"459","author":"Heintzman","year":"2009","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nature13415","article-title":"Comparative analysis of metazoan chromatin organization","volume":"512","author":"Ho","year":"2014","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B16","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nmeth.1937","article-title":"Unsupervised pattern discovery in human chromatin structure through genomic segmentation","volume":"9","author":"Hoffman","year":"2012","journal-title":"Nat. Methods"},{"key":"2023020202145602000_btv117-B17","doi-asserted-by":"crossref","first-page":"e1000201","DOI":"10.1371\/journal.pcbi.1000201","article-title":"ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome","volume":"4","author":"Hon","year":"2008","journal-title":"PLoS Comput. Biol."},{"key":"2023020202145602000_btv117-B18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023020202145602000_btv117-B19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF01908075","article-title":"Comparing partitions","volume":"2","author":"Hubert","year":"1985","journal-title":"J. Classification"},{"key":"2023020202145602000_btv117-B20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003233","article-title":"Human genome replication proceeds through four chromatin states","volume":"9","author":"Julienne","year":"2013","journal-title":"PLoS Comput. Biol."},{"key":"2023020202145602000_btv117-B21","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature09725","article-title":"Comprehensive analysis of the chromatin landscape in Drosophila melanogaster","volume":"471","author":"Kharchenko","year":"2011","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ygeno.2013.03.009","article-title":"A tiered hidden Markov model characterizes multi-scale chromatin states","volume":"102","author":"Larson","year":"2013","journal-title":"Genomics"},{"key":"2023020202145602000_btv117-B23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1101\/gr.115519.110","article-title":"Broad chromosomal domains of histone modification patterns in C","volume":"21","author":"Liu","year":"2011","journal-title":"elegans. Genome Res."},{"key":"2023020202145602000_btv117-B24","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nature06008","article-title":"Genome-wide maps of chromatin state in pluripotent and lineage-committed cells","volume":"448","author":"Mikkelsen","year":"2007","journal-title":"Nature"},{"key":"2023020202145602000_btv117-B25","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nrg2641","article-title":"ChIP-seq: advantages and challenges of a maturing technology","volume":"10","author":"Park","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"2023020202145602000_btv117-B26","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1080\/01621459.1971.10482356","article-title":"Objective criteria for the evaluation of clustering methods","volume":"66","author":"Rand","year":"1971","journal-title":"J. Am. Stat. Assoc."},{"key":"2023020202145602000_btv117-B27","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1038\/emboj.2011.103","article-title":"Integrative epigenomic mapping defines four main chromatin states in Arabidopsis: organization of the Arabidopsis epigenome","volume":"30","author":"Roudier","year":"2011","journal-title":"EMBO J."},{"key":"2023020202145602000_btv117-B28","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1534\/genetics.112.140228","article-title":"Robust estimation of local genetic ancestry in admixed populations using a nonparametric Bayesian approach","volume":"191","author":"Sohn","year":"2012","journal-title":"Genetics"},{"key":"2023020202145602000_btv117-B29","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1198\/016214506000000302","article-title":"Hierarchical Dirichlet processes","volume":"101","author":"Teh","year":"2006","journal-title":"J. Am. Stat. Assoc."},{"key":"2023020202145602000_btv117-B30","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1145\/1390156.1390293","article-title":"Beam sampling for the infinite hidden Markov model","volume-title":"Proceedings of the 25th International Conference on Machine Learning","author":"Van Gael","year":"2008"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/13\/2066\/49034989\/bioinformatics_31_13_2066.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/13\/2066\/49034989\/bioinformatics_31_13_2066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T14:27:28Z","timestamp":1717770448000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/13\/2066\/196202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,27]]},"references-count":30,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2015,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv117","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,7,1]]},"published":{"date-parts":[[2015,2,27]]}}}