{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:42:27Z","timestamp":1767897747783,"version":"3.49.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2016,10,28]],"date-time":"2016-10-28T00:00:00Z","timestamp":1477612800000},"content-version":"vor","delay-in-days":192,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Computational prediction of transcription factor (TF) binding sites in the genome remains a challenging task. Here, we present Romulus, a novel computational method for identifying individual TF binding sites from genome sequence information and cell-type\u2013specific experimental data, such as DNase-seq. It combines the strengths of previous approaches, and improves robustness by reducing the number of free parameters in the model by an order of magnitude.<\/jats:p>\n               <jats:p>Results: We show that Romulus significantly outperforms existing methods across three sources of DNase-seq data, by assessing the performance of these tools against ChIP-seq profiles. The difference was particularly significant when applied to binding site prediction for low-information-content motifs. Our method is capable of inferring multiple binding modes for a single TF, which differ in their DNase I cut profile. Finally, using the model learned by Romulus and ChIP-seq data, we introduce Binding in Closed Chromatin (BCC) as a quantitative measure of TF pioneer factor activity. Uniquely, our measure quantifies a defining feature of pioneer factors, namely their ability to bind closed chromatin.<\/jats:p>\n               <jats:p>Availability and Implementation: Romulus is freely available as an R package at http:\/\/github.com\/ajank\/Romulus .<\/jats:p>\n               <jats:p>Contact: \u00a0ajank@mimuw.edu.pl<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw209","type":"journal-article","created":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T01:30:19Z","timestamp":1461115819000},"page":"2419-2426","source":"Crossref","is-referenced-by-count":21,"title":["Romulus: robust multi-state identification \nof transcription factor binding sites from \nDNase-seq data"],"prefix":"10.1093","volume":"32","author":[{"given":"Aleksander","family":"Jankowski","sequence":"first","affiliation":[{"name":"1 Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warszawa, Poland"},{"name":"2 Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore"}]},{"given":"Jerzy","family":"Tiuryn","sequence":"additional","affiliation":[{"name":"1 Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, 02-097 Warszawa, Poland"}]},{"given":"Shyam","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"2 Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore"}]}],"member":"286","published-online":{"date-parts":[[2016,4,19]]},"reference":[{"key":"2023020112542873600_btw209-B1","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1093\/nar\/gkv195","article-title":"Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism","volume":"43","author":"Blatti","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023020112542873600_btw209-B2","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":"Bernstein","year":"2012","journal-title":"Nature"},{"key":"2023020112542873600_btw209-B3","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1093\/bioinformatics\/btn480","article-title":"F-Seq: a feature density estimator for high-throughput sequence tags","volume":"24","author":"Boyle","year":"2008","journal-title":"Bioinformatics"},{"key":"2023020112542873600_btw209-B4","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1101\/gad.200436.112","article-title":"The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling","volume":"26","author":"Budry","year":"2012","journal-title":"Genes Dev"},{"key":"2023020112542873600_btw209-B5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1101\/gr.4074106","article-title":"Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS)","volume":"16","author":"Crawford","year":"2006","journal-title":"Genome Res"},{"key":"2023020112542873600_btw209-B6","first-page":"233","author":"Davis","year":"2006"},{"key":"2023020112542873600_btw209-B7","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.molcel.2012.07.030","article-title":"A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals","volume":"47","author":"Garber","year":"2012","journal-title":"Mol. 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