{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:38:45Z","timestamp":1740184725691,"version":"3.37.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 HG005998"],"award-info":[{"award-number":["R01 HG005998"]}]},{"name":"National Science Foundation (NSF) CAREER","award":["DBI-0546275"],"award-info":[{"award-number":["DBI-0546275"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 GM071966","R24OD011194"],"award-info":[{"award-number":["R01 GM071966","R24OD011194"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institute For Advanced Research in the Genetic Networks group"},{"DOI":"10.13039\/100008730","name":"Norwegian Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Radiumhospitalets Legater"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Breast cancer consists of multiple distinct tumor subtypes, and results from epigenetic and genetic aberrations that give rise to distinct transcriptional profiles. Despite previous efforts to understand transcriptional deregulation through transcription factor networks, the transcriptional mechanisms leading to subtypes of the disease remain poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We used a sophisticated computational search of thousands of expression datasets to define extended signatures of distinct breast cancer subtypes. Using ENCODE ChIP-seq data of surrogate cell lines and motif analysis we observed that these subtypes are determined by a distinct repertoire of lineage-specific transcription factors. Furthermore, specific pattern and abundance of copy number and DNA methylation changes at these TFs and targets, compared to other genes and to normal cells were observed. Overall, distinct transcriptional profiles are linked to genetic and epigenetic alterations at lineage-specific transcriptional regulators in breast cancer subtypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The analysis code and data are deposited at https:\/\/bitbucket.org\/qzhu\/breast.cancer.tf\/.<\/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\/btz709","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T19:33:22Z","timestamp":1568316802000},"page":"994-999","source":"Crossref","is-referenced-by-count":8,"title":["Subtype-specific transcriptional regulators in breast tumors subjected to genetic and epigenetic alterations"],"prefix":"10.1093","volume":"36","author":[{"given":"Qian","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute , Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Tekpli","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet , Oslo, Norway"},{"name":"Division of Medicine, Department of Clinical Molecular Biology (EpiGen) , Akershus University Hospital, L\u00f8renskog, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga G","family":"Troyanskaya","sequence":"additional","affiliation":[{"name":"Department of Computer Science , USA"},{"name":"Lewis-Siegler Institute of Integrative Genomics, Princeton University , Princeton, NJ 08540, USA"},{"name":"Simons Foundation, Flatiron Institute , New York, NY 10010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vessela N","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet , Oslo, Norway"},{"name":"Division of Medicine, Department of Clinical Molecular Biology (EpiGen) , Akershus University Hospital, L\u00f8renskog, Norway"},{"name":"Institute for Clinical Medicine, University of Oslo , Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"2023013110155273600_btz709-B1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nature14289","article-title":"Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice","volume":"521","author":"Adam","year":"2015","journal-title":"Nature"},{"key":"2023013110155273600_btz709-B2","doi-asserted-by":"crossref","first-page":"R126","DOI":"10.1186\/gb-2013-14-11-r126","article-title":"Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors","volume":"14","author":"Aure","year":"2013","journal-title":"Genome Biol"},{"key":"2023013110155273600_btz709-B3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"Cancer","year":"2012","journal-title":"Nature"},{"key":"2023013110155273600_btz709-B4","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature10983","article-title":"The genomic and transcriptomic architecture of 2, 000 breast tumours reveals novel subgroups","volume":"486","author":"Curtis","year":"2012","journal-title":"Nature"},{"key":"2023013110155273600_btz709-B5","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":"Dunham","year":"2012","journal-title":"Nature"},{"key":"2023013110155273600_btz709-B6","doi-asserted-by":"crossref","first-page":"48.","DOI":"10.1186\/1471-2105-10-48","article-title":"GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists","volume":"10","author":"Eden","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023013110155273600_btz709-B8","first-page":"435.","article-title":"Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis","volume":"15","author":"Fleischer","year":"2014","journal-title":"Genome Biol"},{"key":"2023013110155273600_btz709-B7","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00510-x","article-title":"DNA methylation at enhancers identifies distinct breast cancer lineages","volume":"8","author":"Fleischer","year":"2017","journal-title":"Nat. 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