{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:08:00Z","timestamp":1790827680429,"version":"4.1.0"},"reference-count":62,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["Clinical PhD and PhD funding"],"award-info":[{"award-number":["Clinical PhD and PhD funding"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["Programme grant and studentship 103857\/Z\/14\/Z"],"award-info":[{"award-number":["Programme grant and studentship 103857\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett\u2019s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.<\/jats:p>","DOI":"10.7554\/elife.57189","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T08:01:11Z","timestamp":1599120071000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57189","source":"Crossref","is-referenced-by-count":26,"title":["Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-9668","authenticated-orcid":true,"given":"Connor","family":"Rogerson","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Ogden","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Britton","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The OCCAMS Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-6710","authenticated-orcid":true,"given":"Yeng","family":"Ang","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"},{"name":"GI Science Centre, Salford Royal NHS FT, University of Manchester, Salford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6380-321X","authenticated-orcid":true,"given":"Andrew D","family":"Sharrocks","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18035-1","article-title":"ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation","volume":"11","author":"Bentsen","year":"2020","journal-title":"Nature Communications"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08886-8","article-title":"Overexpression of claspin and timeless protects Cancer cells from replication stress in a checkpoint-independent manner","volume":"10","author":"Bianco","year":"2019","journal-title":"Nature Communications"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1053\/j.gastro.2019.01.263","article-title":"Systems biology analyses show hyperactivation of transforming growth Factor-\u03b2 and JNK signaling pathways in esophageal Cancer","volume":"156","author":"Blum","year":"2019","journal-title":"Gastroenterology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006879","article-title":"Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma","volume":"13","author":"Britton","year":"2017","journal-title":"PLOS Genetics"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.gde.2012.08.001","article-title":"Barrett's metaplasia as a paradigm for understanding the development of cancer","volume":"22","author":"Burke","year":"2012","journal-title":"Current Opinion in Genetics & Development"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nature20805","article-title":"Integrated genomic characterization of oesophageal carcinoma","volume":"541","author":"Cancer Genome Atlas Research Network","year":"2017","journal-title":"Nature"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"6567","DOI":"10.1038\/sj.onc.1205817","article-title":"A possible tumor suppressor role of the KLF5 transcription factor in human breast Cancer","volume":"21","author":"Chen","year":"2002","journal-title":"Oncogene"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1136\/gutjnl-2019-318325","article-title":"Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in oesophageal adenocarcinoma","volume":"69","author":"Chen","year":"2020","journal-title":"Gut"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1136\/gutjnl-2013-306596","article-title":"Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric Cancer development","volume":"64","author":"Chia","year":"2015","journal-title":"Gut"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1053\/j.gastro.2017.07.046","article-title":"The epidemiology of esophageal adenocarcinoma","volume":"154","author":"Coleman","year":"2018","journal-title":"Gastroenterology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/nmeth.4396","article-title":"An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues","volume":"14","author":"Corces","year":"2017","journal-title":"Nature Methods"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav1898","article-title":"The chromatin accessibility landscape of primary human cancers","volume":"362","author":"Corces","year":"2018","journal-title":"Science"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1016\/j.athoracsur.2004.05.037","article-title":"ERBB2 amplifications in esophageal adenocarcinoma","volume":"78","author":"Dahlberg","year":"2004","journal-title":"The Annals of Thoracic Surgery"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004994","article-title":"Discovery of transcription factors and regulatory regions driving in vivo tumor development by ATAC-seq and FAIRE-seq open chromatin profiling","volume":"11","author":"Davie","year":"2015","journal-title":"PLOS Genetics"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.cell.2016.05.052","article-title":"Nfib promotes metastasis through a widespread increase in chromatin accessibility","volume":"166","author":"Denny","year":"2016","journal-title":"Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166438","article-title":"An alternative approach to ChIP-Seq normalization enables detection of Genome-Wide changes in histone H3 lysine 27 trimethylation upon EZH2 inhibition","volume":"11","author":"Egan","year":"2016","journal-title":"PLOS ONE"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"International Journal of Cancer"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/s41588-018-0331-5","article-title":"The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic","volume":"51","author":"Frankell","year":"2019","journal-title":"Nature Genetics"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171824","article-title":"A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma","volume":"12","author":"Hassan","year":"2017","journal-title":"PLOS ONE"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1053\/j.gastro.2017.12.005","article-title":"Kr\u00fcppel-like factor 5, increased in pancreatic ductal adenocarcinoma, promotes proliferation, Acinar-to-Ductal metaplasia, pancreatic intraepithelial neoplasia, and tumor growth in mice","volume":"154","author":"He","year":"2018","journal-title":"Gastroenterology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/nmeth.2812","article-title":"E-CRISP: fast CRISPR target site identification","volume":"11","author":"Heigwer","year":"2014","journal-title":"Nature Methods"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Molecular Cell"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.1158\/0008-5472.CAN-12-1119","article-title":"Regulation of ERBB2 receptor by t-DARPP mediates trastuzumab resistance in human esophageal adenocarcinoma","volume":"72","author":"Hong","year":"2012","journal-title":"Cancer Research"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.30506","article-title":"Chromatin accessibility underlies synthetic lethality of SWI\/SNF subunits in ARID1A-mutant cancers","volume":"6","author":"Kelso","year":"2017","journal-title":"eLife"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Research"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nature Methods"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"4251","DOI":"10.1073\/pnas.1011989109","article-title":"Activation of GATA binding protein 6 (GATA6) sustains oncogenic lineage-survival in esophageal adenocarcinoma","volume":"109","author":"Lin","year":"2012","journal-title":"PNAS"},{"key":"bib33","doi-asserted-by":"publisher","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 Biology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1158\/1541-7786.MCR-17-0332","article-title":"Novel aberrations uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing","volume":"15","author":"Maag","year":"2017","journal-title":"Molecular Cancer Research"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-019-10898-3","article-title":"Patient-specific Cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma","volume":"10","author":"Mourikis","year":"2019","journal-title":"Nature Communications"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1016\/j.febslet.2005.07.053","article-title":"Kr\u00fcppel-like factor 5 promotes mitosis by activating the cyclin B1\/Cdc2 complex during oncogenic Ras-mediated transformation","volume":"579","author":"Nandan","year":"2005","journal-title":"FEBS Letters"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1158\/1541-7786.MCR-16-0123","article-title":"Transcription factor KLF5 binds a cyclin E1 polymorphic intronic enhancer to confer increased bladder Cancer risk","volume":"14","author":"Pattison","year":"2016","journal-title":"Molecular Cancer Research"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/S0140-6736(12)60643-6","article-title":"Oesophageal carcinoma","volume":"381","author":"Pennathur","year":"2013","journal-title":"The Lancet"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9471","article-title":"BAP1 promotes breast Cancer cell proliferation and metastasis by deubiquitinating KLF5","volume":"6","author":"Qin","year":"2015","journal-title":"Nature Communications"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ram\u00edrez","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1101\/839142","article-title":"Predicting master transcription factors from pan-cancer expression data","volume-title":"bioRxiv","author":"Reddy","year":"2019"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11938","article-title":"Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks","volume":"7","author":"Rendeiro","year":"2016","journal-title":"Nature Communications"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1101\/gr.243345.118","article-title":"Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its precancerous precursor state","volume":"29","author":"Rogerson","year":"2019","journal-title":"Genome Research"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/ng.3357","article-title":"Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma","volume":"47","author":"Ross-Innes","year":"2015","journal-title":"Nature Genetics"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.48","article-title":"Oesophageal cancer","volume":"3","author":"Smyth","year":"2017","journal-title":"Nature Reviews Disease Primers"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1056\/NEJMra1314704","article-title":"Barrett's esophagus","volume":"371","author":"Spechler","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/ng.3343","article-title":"Paired exome analysis of Barrett's esophagus and adenocarcinoma","volume":"47","author":"Stachler","year":"2015","journal-title":"Nature Genetics"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.gastro.2018.03.047","article-title":"Detection of mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma","volume":"155","author":"Stachler","year":"2018","journal-title":"Gastroenterology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"PNAS"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1593\/neo.122126","article-title":"Restoring KLF5 in esophageal squamous cell Cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival","volume":"15","author":"Tarapore","year":"2013","journal-title":"Neoplasia"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06258-2","article-title":"Analysis of chromatin accessibility uncovers TEAD1 as a regulator of migration in human glioblastoma","volume":"9","author":"Tome-Garcia","year":"2018","journal-title":"Nature Communications"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nature Protocols"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"17685","DOI":"10.18632\/oncotarget.3779","article-title":"The interplay between TEAD4 and KLF5 promotes breast Cancer partially through inhibiting the transcription of p27Kip1","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/ng.3013","article-title":"Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis","volume":"46","author":"Weaver","year":"2014","journal-title":"Nature Genetics"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-015-0339-8","article-title":"Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma","volume":"14","author":"Wiseman","year":"2015","journal-title":"Molecular Cancer"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10380","article-title":"Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion","volume":"7","author":"Yamamoto","year":"2016","journal-title":"Nature Communications"},{"key":"bib58","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biology"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1158\/2159-8290.CD-17-0532","article-title":"Somatic superenhancer duplications and hotspot mutations lead to oncogenic activation of the KLF5 transcription factor","volume":"8","author":"Zhang","year":"2018","journal-title":"Cancer Discovery"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1016\/j.ajpath.2012.02.025","article-title":"YAP promotes breast cell proliferation and survival partially through stabilizing the KLF5 transcription factor","volume":"180","author":"Zhi","year":"2012","journal-title":"The American Journal of Pathology"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nature Communications"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36168-8","article-title":"Genomic and regulatory characteristics of significant transcription factors in colorectal Cancer metastasis","volume":"8","author":"Zhou","year":"2018","journal-title":"Scientific Reports"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/57189\/elife-57189-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/57189\/elife-57189-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/57189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:08:57Z","timestamp":1697058537000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/57189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":62,"alternative-id":["10.7554\/eLife.57189"],"URL":"https:\/\/doi.org\/10.7554\/elife.57189","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"accession","id":"E-MTAB-5169","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-6751","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-6756","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-6758","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-4054","asserted-by":"subject"},{"id-type":"accession","id":"TCGA-ESCA","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"E-MTAB-8447","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8446","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8568","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8584","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8576","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8579","asserted-by":"subject"},{"id-type":"accession","id":"EGAD00001005915","asserted-by":"subject"},{"id-type":"accession","id":"E-MTAB-8994","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.57189.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.57189.sa2","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.02.10.941872","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]},"article-number":"e57189"}}