{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:49:42Z","timestamp":1782805782056,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Epigenome Project (DEEP"},{"name":"German Science Ministry","award":["01KU1216A"],"award-info":[{"award-number":["01KU1216A"]}]},{"name":"DFG Clusters of Excellence on Multimodal Computing and Interaction","award":["EXC248"],"award-info":[{"award-number":["EXC248"]}]},{"DOI":"10.13039\/501100021703","name":"Cardio Pulmonary Institute","doi-asserted-by":"crossref","award":["EXC 2026"],"award-info":[{"award-number":["EXC 2026"]}],"id":[{"id":"10.13039\/501100021703","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The generation of genome-wide maps of histone modifications using chromatin immunoprecipitation sequencing is a standard approach to dissect the complexity of the epigenome. Interpretation and differential analysis of histone datasets remains challenging due to regulatory meaningful co-occurrences of histone marks and their difference in genomic spread. To ease interpretation, chromatin state segmentation maps are a commonly employed abstraction combining individual histone marks. We developed the tool SCIDDO as a fast, flexible and statistically sound method for the differential analysis of chromatin state segmentation maps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate the utility of SCIDDO in a comparative analysis that identifies differential chromatin domains (DCD) in various regulatory contexts and with only moderate computational resources. We show that the identified DCDs correlate well with observed changes in gene expression and can recover a substantial number of differentially expressed genes (DEGs). We showcase SCIDDO\u2019s ability to directly interrogate chromatin dynamics, such as enhancer switches in downstream analysis, which simplifies exploring specific questions about regulatory changes in chromatin. By comparing SCIDDO to competing methods, we provide evidence that SCIDDO\u2019s performance in identifying DEGs via differential chromatin marking is more stable across a range of cell-type comparisons and parameter cut-offs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The SCIDDO source code is openly available under github.com\/ptrebert\/sciddo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa960","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T16:55:27Z","timestamp":1605718527000},"page":"1198-1205","source":"Crossref","is-referenced-by-count":8,"title":["Fast detection of differential chromatin domains with SCIDDO"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-532X","authenticated-orcid":false,"given":"Peter","family":"Ebert","sequence":"first","affiliation":[{"name":"Institute for Medical Biometry and Bioinformatics, Heinrich Heine University , 40225 D\u00fcsseldorf, Germany"},{"name":"Max Planck Institute for Informatics, Saarland Informatics Campus , 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-3656","authenticated-orcid":false,"given":"Marcel H","family":"Schulz","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Informatics, Saarland Informatics Campus , 66123 Saarbr\u00fccken, Germany"},{"name":"Cluster of Excellence on Multimodal Computing and Interaction, Saarland Informatics Campus , 66123 Saarbr\u00fccken, Germany"},{"name":"Institute for Cardiovascular Regeneration, Goethe University , 60590 Frankfurt am Main, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Rhein-Main , 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"2023051706054438700_btaa960-B1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nbt.2153","article-title":"BLUEPRINT to decode the epigenetic signature written in blood","volume":"30","author":"Adams","year":"2012","journal-title":"Nat. Biotechnol"},{"key":"2023051706054438700_btaa960-B2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol"},{"key":"2023051706054438700_btaa960-B3","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":"2023051706054438700_btaa960-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":"2023051706054438700_btaa960-B5","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2007.01.033","article-title":"The mammalian epigenome","volume":"128","author":"Bernstein","year":"2007","journal-title":"Cell"},{"key":"2023051706054438700_btaa960-B6","doi-asserted-by":"crossref","first-page":"9244","DOI":"10.1093\/nar\/gkx618","article-title":"Automatic identification of informative regions with epigenomic changes associated to hematopoiesis","volume":"45","author":"Carrillo-de Santa-Pau","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2023051706054438700_btaa960-B7","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac separates active from poised enhancers and predicts developmental state","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706054438700_btaa960-B8","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":"2023051706054438700_btaa960-B9","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nbt.3157","article-title":"Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues","volume":"33","author":"Ernst","year":"2015","journal-title":"Nat. Biotechnol"},{"key":"2023051706054438700_btaa960-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":"2023051706054438700_btaa960-B11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/ng1966","article-title":"Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome","volume":"39","author":"Heintzman","year":"2007","journal-title":"Nat. Genet"},{"key":"2023051706054438700_btaa960-B12","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nrm2727","article-title":"Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington\u2019s canal","volume":"10","author":"Hemberger","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023051706054438700_btaa960-B13","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":"2023051706054438700_btaa960-B14","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1093\/bioinformatics\/bty075","article-title":"Chromswitch: a flexible method to detect chromatin state switches","volume":"34","author":"Jessa","year":"2018","journal-title":"Bioinformatics"},{"key":"2023051706054438700_btaa960-B15","doi-asserted-by":"crossref","first-page":"6789","DOI":"10.1073\/pnas.1204398110","article-title":"Differential principal component analysis of chip-seq","volume":"110","author":"Ji","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706054438700_btaa960-B16","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cell.2007.01.029","article-title":"The epigenomics of cancer","volume":"128","author":"Jones","year":"2007","journal-title":"Cell"},{"key":"2023051706054438700_btaa960-B17","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1073\/pnas.0909344107","article-title":"Histone modification levels are predictive for gene expression","volume":"107","author":"Karli\u0107","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706054438700_btaa960-B18","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1073\/pnas.87.6.2264","article-title":"Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes","volume":"87","author":"Karlin","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706054438700_btaa960-B19","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1214\/aos\/1176347616","article-title":"Statistical composition of high-scoring segments from molecular sequences","volume":"18","author":"Karlin","year":"1990","journal-title":"Ann. Stat"},{"key":"2023051706054438700_btaa960-B20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"2023051706054438700_btaa960-B21","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrm3543","article-title":"Leveling Waddington: the emergence of direct programming and the loss of cell fate hierarchies","volume":"14","author":"Ladewig","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023051706054438700_btaa960-B22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1109\/18.61115","article-title":"Divergence measures based on the Shannon entropy","volume":"37","author":"Lin","year":"1991","journal-title":"IEEE Trans. Inf. Theory"},{"key":"2023051706054438700_btaa960-B23","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2023051706054438700_btaa960-B24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.tig.2016.03.001","article-title":"Evolution of epigenetic regulation in vertebrate genomes","volume":"32","author":"Lowdon","year":"2016","journal-title":"Trends Genet"},{"key":"2023051706054438700_btaa960-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-015-0708-z","article-title":"Chromatin segmentation based on a probabilistic model for read counts explains a large portion of the epigenome","volume":"16","author":"Mammana","year":"2015","journal-title":"Genome Biol"},{"key":"2023051706054438700_btaa960-B26","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":"2023051706054438700_btaa960-B27","first-page":"3.5.1","volume-title":"Curr. Protoc. Bioinformatics","author":"Pearson","year":"2013"},{"key":"2023051706054438700_btaa960-B28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.molcel.2014.06.015","article-title":"Enhancer function: mechanistic and genome-wide insights come together","volume":"55","author":"Plank","year":"2014","journal-title":"Mol. Cell"},{"key":"2023051706054438700_btaa960-B29","first-page":"234","article-title":"A linear time algorithm for finding all maximal scoring subsequences","author":"Ruzzo","year":"1999","journal-title":"Proc. Int. Conf. Intell. Syst. Mol. Biol"},{"key":"2023051706054438700_btaa960-B30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13059-015-0598-0","article-title":"Spectacle: fast chromatin state annotation using spectral learning","volume":"16","author":"Song","year":"2015","journal-title":"Genome Biol"},{"key":"2023051706054438700_btaa960-B31","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","year":"2012","journal-title":"Nature"},{"key":"2023051706054438700_btaa960-B32","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nature07730","article-title":"ChIP-seq accurately predicts tissue-specific activity of enhancers","volume":"457","author":"Visel","year":"2009","journal-title":"Nature"},{"key":"2023051706054438700_btaa960-B33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13072-016-0079-z","article-title":"Epigenetic dynamics of monocyte-to-macrophage differentiation","volume":"9","author":"Wallner","year":"2016","journal-title":"Epigenetics Chromatin"},{"key":"2023051706054438700_btaa960-B34","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1038\/ncomms8973","article-title":"Systematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type","volume":"6","author":"Yen","year":"2015","journal-title":"Nat. Commun"},{"key":"2023051706054438700_btaa960-B35","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1093\/bioinformatics\/btu372","article-title":"PePr: a peak-calling prioritization pipeline to identify consistent or differential peaks from replicated ChIP-Seq data","volume":"30","author":"Zhang","year":"2014","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/9\/1198\/50359562\/btaa960.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa960\/34557521\/btaa960.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/9\/1198\/50359562\/btaa960.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T02:12:36Z","timestamp":1684289556000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/9\/1198\/6000228"}},"subtitle":[],"editor":[{"given":"Birol","family":"Inanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,24]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,6,9]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa960","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/441766","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2020,11,24]]}}}