{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:30:04Z","timestamp":1773307804389,"version":"3.50.1"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2259,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation.<\/jats:p>\n               <jats:p>Results: We tested this hypothesis using a multi-evidence approach for predicting binding sites. As a training\/test dataset, we used ChIP-Seq-derived TF binding site locations for five TFs in activated murine macrophages. Our model combined TF binding site motif scanning with evidence from sequence-based sources and from HAc ChIP-Seq data, using a weighted sum of thresholded scores. We find that using HAc data significantly improves the performance of motif-based TF binding site prediction. Furthermore, we find that within regions of high HAc, local minima of the HAc ChIP-Seq signal are particularly strongly correlated with TF binding locations. Our model, using motif scanning and HAc local minima, improves the sensitivity for TF binding site prediction by \u223c50% over a model based on motif scanning alone, at a false positive rate cutoff of 0.01.<\/jats:p>\n               <jats:p>Availability: The data and software source code for model training and validation are freely available online at http:\/\/magnet.systemsbiology.net\/hac.<\/jats:p>\n               <jats:p>Contact: \u00a0aderem@systemsbiology.org; ishmulevich@systemsbiology.org<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq405","type":"journal-article","created":{"date-parts":[[2010,7,28]],"date-time":"2010-07-28T00:49:19Z","timestamp":1280278159000},"page":"2071-2075","source":"Crossref","is-referenced-by-count":55,"title":["Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites"],"prefix":"10.1093","volume":"26","author":[{"given":"Stephen A.","family":"Ramsey","sequence":"first","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Theo A.","family":"Knijnenburg","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Kathleen A.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Daniel E.","family":"Zak","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Mark","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Elizabeth S.","family":"Gold","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Carrie D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Aaron E.","family":"Lampano","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Vladimir","family":"Litvak","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Garnet","family":"Navarro","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Tetyana","family":"Stolyar","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Alan","family":"Aderem","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]},{"given":"Ilya","family":"Shmulevich","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, 1441 North 34th Street, Seattle, WA, 98103, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,7,27]]},"reference":[{"key":"2023012508001986900_B1","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1096\/fj.05-5360com","article-title":"LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression","volume":"20","author":"Aung","year":"2006","journal-title":"FASEB J."},{"key":"2023012508001986900_B2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature05915","article-title":"The complex language of chromatin regulation during transcription","volume":"447","author":"Berger","year":"2007","journal-title":"Nature"},{"key":"2023012508001986900_B3","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1371\/journal.pcbi.0020070","article-title":"Integrated assessment and prediction of transcription factor binding","volume":"2","author":"Beyer","year":"2006","journal-title":"PLoS Comput. 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