{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:49:17Z","timestamp":1768808957220,"version":"3.49.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T00:00:00Z","timestamp":1512518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["P30 ES020957"],"award-info":[{"award-number":["P30 ES020957"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30 CA022453"],"award-info":[{"award-number":["P30 CA022453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Epigenetic mechanisms are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in an aggressive subtype known as triple negative breast cancer (TNBC). To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We proceeded to develop an approach to integrate novel Pvu-sequencing and RNA-sequencing data. The result of our approach to merge genome-wide, high-throughput TNBC cell line datasets to identify significant, concordant 5hmC and mRNA changes in response to antioxidant treatment produced a gene set with relevance to cancer stem cell function. Moreover, we have established a method that will be useful for continued research of 5hmC in TNBC cells and tissue samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Data are available at Gene Expression Omnibus (GEO) under accession number GSE103850.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx777","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T15:44:20Z","timestamp":1512143060000},"page":"1441-1447","source":"Crossref","is-referenced-by-count":11,"title":["Integrating 5hmC and gene expression data to infer regulatory mechanisms"],"prefix":"10.1093","volume":"34","author":[{"given":"Cristina","family":"Mitrea","sequence":"first","affiliation":[{"name":"Department of Oncology, Wayne State University, Detroit, MI, USA"},{"name":"Department of Computer Science, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanga","family":"Wijesinghe","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University, Detroit, MI, USA"},{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Dyson","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University, Detroit, MI, USA"},{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ad\u00e9le","family":"Kruger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas M","family":"Ruden","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA"},{"name":"Department of Pharmacology, Wayne State University, Detroit, MI, USA"},{"name":"Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorin","family":"Dr\u0103ghici","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Wayne State University, Detroit, MI, USA"},{"name":"Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliccia","family":"Bollig-Fischer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University, Detroit, MI, USA"},{"name":"Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,6]]},"reference":[{"key":"2023012713021812400_btx777-B1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/cpbi.24","article-title":"Identifying significantly impacted pathways and putative mechanisms with iPathwayGuide","volume":"57","author":"Ahsan","year":"2017","journal-title":"Curr Protoc Bioinformatics"},{"key":"2023012713021812400_btx777-B2","doi-asserted-by":"crossref","first-page":"R106.","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2023012713021812400_btx777-B3","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"2023012713021812400_btx777-B4","doi-asserted-by":"crossref","first-page":"44125","DOI":"10.1038\/srep44125","article-title":"Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity","volume":"7","author":"Bao","year":"2017","journal-title":"Sci. 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