{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:53:23Z","timestamp":1770432803520,"version":"3.49.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Epigenetic modifications are one of the critical factors to regulate gene expression and genome function. Among different epigenetic modifications, the differential histone modification sites (DHMSs) are of great interest to study the dynamic nature of epigenetic and gene expression regulations among various cell types, stages or environmental responses. To capture the histone modifications at whole genome scale, ChIP-seq technology is becoming a robust and comprehensive approach. Thus the DHMSs are potentially identifiable by comparing two ChIP-seq libraries. However, little has been addressed on this issue in literature.<\/jats:p>\n               <jats:p>Results: Aiming at identifying DHMSs, we propose an approach called ChIPDiff for the genome-wide comparison of histone modification sites identified by ChIP-seq. Based on the observations of ChIP fragment counts, the proposed approach employs a hidden Markov model (HMM) to infer the states of histone modification changes at each genomic location. We evaluated the performance of ChIPDiff by comparing the H3K27me3 modification sites between mouse embryonic stem cell (ESC) and neural progenitor cell (NPC). We demonstrated that the H3K27me3 DHMSs identified by our approach are of high sensitivity, specificity and technical reproducibility. ChIPDiff was further applied to uncover the differential H3K4me3 and H3K36me3 sites between different cell states. Interesting biological discoveries were achieved from such comparison in our study.<\/jats:p>\n               <jats:p>Availability: \u00a0http:\/\/cmb.gis.a-star.edu.sg\/ChIPSeq\/tools.htm<\/jats:p>\n               <jats:p>Contact: \u00a0asflin@ntu.edu.sg; sungk@gis.a-star.edu.sg<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary methods and data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn402","type":"journal-article","created":{"date-parts":[[2008,7,31]],"date-time":"2008-07-31T00:24:08Z","timestamp":1217463848000},"page":"2344-2349","source":"Crossref","is-referenced-by-count":127,"title":["An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data"],"prefix":"10.1093","volume":"24","author":[{"given":"Han","family":"Xu","sequence":"first","affiliation":[{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"},{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Lin","family":"Wei","sequence":"additional","affiliation":[{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wing-Kin","family":"Sung","sequence":"additional","affiliation":[{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"},{"name":"1 Computational & Mathematical Biology Group, Genome Institute of Singapore, 138672 Singapore, 2School of Computer Engineering, Nanyang Technological University, 637553 Singapore, 3Genome Technology & Biology Group, Genome Institute of Singapore, 138672 Singapore and 4School of Computing, National University of Singapore, 117543 Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,29]]},"reference":[{"key":"2023020211252753900_B1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-resolution profiling of histone methylations in the human genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"2023020211252753900_B2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1214\/aoms\/1177697196","article-title":"A maximization technique occurring in the statistical analysis of probabilistic functions of Markov chains","volume":"41","author":"Baum","year":"1970","journal-title":"Ann. Math. Statist."},{"key":"2023020211252753900_B3","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":"2023020211252753900_B4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature04733","article-title":"Polycomb complexes repress developmental regulators in murine embryonic stem cells","volume":"441","author":"Boyer","year":"2006","journal-title":"Nature"},{"key":"2023020211252753900_B5","first-page":"1","article-title":"Quantitative analysis of nucleic acids \u2013 the last few years of progress","volume":"37","author":"Ding","year":"2004","journal-title":"J. Biochem. Mol. Biol."},{"key":"2023020211252753900_B6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1634\/stemcells.2006-0383","article-title":"Concise review: epigenetic mechanism contribute to pluripotency and cell lineage determination of embryonic stem cells","volume":"25","author":"Gan","year":"2007","journal-title":"Stem Cell"},{"key":"2023020211252753900_B7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cell.2007.05.042","article-title":"A chromatin landmark and transcription initiation at most promoters in human cells","volume":"130","author":"Guenther","year":"2007","journal-title":"Cell"},{"key":"2023020211252753900_B8","first-page":"1041","article-title":"Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions","volume":"119","author":"Impey","year":"2004","journal-title":"Cell"},{"key":"2023020211252753900_B9","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1126\/science.1141319","article-title":"Genome-wide mapping of in vivo protein-DNA interactions","volume":"316","author":"Johnson","year":"2007","journal-title":"Science"},{"key":"2023020211252753900_B10","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.genom.7.080505.115634","article-title":"Genome-wide analysis of protein-DNA interactions","volume":"7","author":"Kim","year":"2006","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"issue":"Suppl. 1","key":"2023020211252753900_B11","doi-asserted-by":"crossref","first-page":"i274","DOI":"10.1093\/bioinformatics\/bti1046","article-title":"A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences","volume":"21","author":"Li","year":"2005","journal-title":"Bioinformatics (ISMB2005)"},{"key":"2023020211252753900_B12","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nmeth0807-613","article-title":"ChIP-seq: welcome to the new frontier","volume":"4","author":"Mardis","year":"2007","journal-title":"Nat. Methods"},{"key":"2023020211252753900_B13","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/nrm1761","article-title":"The diverse functions of histone lysine methylation","volume":"6","author":"Martin","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2023020211252753900_B14","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1158\/0008-5472.CAN-05-2481","article-title":"Silenced tumor suppressor genes reactivated by DNA demthylation do not return to a fully euchromatic chromatin state","volume":"66","author":"McGarvey","year":"2006","journal-title":"Cancer Res."},{"key":"2023020211252753900_B15","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":"2023020211252753900_B16","doi-asserted-by":"crossref","first-page":"D501","DOI":"10.1093\/nar\/gki025","article-title":"NCBI reference sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins","volume":"33","author":"Pruitt","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020211252753900_B17","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/ng1032","article-title":"Microarray data normalization and transformation","volume":"32","author":"Quackenbush","year":"2002","journal-title":"Nat. Genet."},{"key":"2023020211252753900_B18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1109\/5.18626","article-title":"A tutorial on hidden Markov models and selected applications in speech recognition","volume":"77","author":"Rabiner","year":"1989","journal-title":"Proc. IEEE"},{"key":"2023020211252753900_B19","volume-title":"Applied Statistical Decision Theory.","author":"Raiffa","year":"2000"},{"key":"2023020211252753900_B20","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nmeth1068","article-title":"Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing","volume":"4","author":"Robertson","year":"2007","journal-title":"Nat. Methods"},{"key":"2023020211252753900_B21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.cell.2005.10.043","article-title":"A global mapping of p53 transcription factor binding sites in the human genome","volume":"124","author":"Wei","year":"2006","journal-title":"Cell"},{"key":"2023020211252753900_B22","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/ng1941","article-title":"Epigenetic stem cell signature in cancer","volume":"39","author":"Widschwendter","year":"2007","journal-title":"Nat. Genet."},{"key":"2023020211252753900_B23","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.stem.2007.08.004","article-title":"Whole-genome mapping of histone h3 lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells","volume":"1","author":"Zhao","year":"2007","journal-title":"Cell Stem Cell"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/20\/2344\/49050271\/bioinformatics_24_20_2344.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/20\/2344\/49050271\/bioinformatics_24_20_2344.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T14:06:28Z","timestamp":1675346788000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/20\/2344\/258202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,29]]},"references-count":23,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2008,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn402","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,10,15]]},"published":{"date-parts":[[2008,7,29]]}}}