{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:08:24Z","timestamp":1783015704189,"version":"3.54.6"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick\u2019s Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01 HG006282"],"award-info":[{"award-number":["R01 HG006282"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000143","name":"NSF | Directorate for Computer & Information Science & Engineering | Division of Computing and Communication Foundations","doi-asserted-by":"publisher","award":["1656201"],"award-info":[{"award-number":["1656201"]}],"id":[{"id":"10.13039\/100000143","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA65438"],"award-info":[{"award-number":["R01 CA65438"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DP1 DK119129"],"award-info":[{"award-number":["DP1 DK119129"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Biomed Eng"],"DOI":"10.1038\/s41551-021-00703-2","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T16:03:25Z","timestamp":1618502605000},"page":"360-376","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Converging genetic and epigenetic drivers of paediatric acute lymphoblastic leukaemia identified by an information-theoretic analysis"],"prefix":"10.1038","volume":"5","author":[{"given":"Michael A.","family":"Koldobskiy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-098X","authenticated-orcid":false,"given":"Garrett","family":"Jenkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-2858","authenticated-orcid":false,"given":"Jordi","family":"Abante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varenka A.","family":"Rodriguez DiBlasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-7945","authenticated-orcid":false,"given":"Elisabet","family":"Pujadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Idrizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakel","family":"Tryggvadottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Callahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-1683","authenticated-orcid":false,"given":"Challice L.","family":"Bonifant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-8195","authenticated-orcid":false,"given":"Karen R.","family":"Rabin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-1069","authenticated-orcid":false,"given":"Patrick A.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6480-0141","authenticated-orcid":false,"given":"Hongkai","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0192-3857","authenticated-orcid":false,"given":"John","family":"Goutsias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8364-1991","authenticated-orcid":false,"given":"Andrew P.","family":"Feinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"703_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1182\/asheducation.V2012.1.389.3798360","volume":"2012","author":"CG Mullighan","year":"2012","unstructured":"Mullighan, C. G. The molecular genetic makeup of acute lymphoblastic leukemia. Hematology Am. Soc. Hematol. Educ. Program 2012, 389\u2013396 (2012).","journal-title":"Hematology Am. Soc. Hematol. Educ. Program"},{"key":"703_CR2","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1056\/NEJMra1400972","volume":"373","author":"SP Hunger","year":"2015","unstructured":"Hunger, S. P. & Mullighan, C. G. Acute lymphoblastic leukemia in children. N. Engl. J. Med. 373, 1541\u20131552 (2015).","journal-title":"N. Engl. J. Med."},{"key":"703_CR3","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature25480","volume":"555","author":"SN Grobner","year":"2018","unstructured":"Grobner, S. N. et al. The landscape of genomic alterations across childhood cancers. Nature 555, 321\u2013327 (2018).","journal-title":"Nature"},{"key":"703_CR4","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nature25795","volume":"555","author":"X Ma","year":"2018","unstructured":"Ma, X. et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature 555, 371\u2013376 (2018).","journal-title":"Nature"},{"key":"703_CR5","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/ng.3291","volume":"47","author":"M Kulis","year":"2015","unstructured":"Kulis, M. et al. Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nat. Genet. 47, 746\u2013756 (2015).","journal-title":"Nat. Genet."},{"key":"703_CR6","doi-asserted-by":"crossref","unstructured":"Figueroa, M.E. et al. Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia. J. Clin. Invest. 123, 3099\u20133111 (2013).","DOI":"10.1172\/JCI66203"},{"key":"703_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-9-r105","volume":"14","author":"J Nordlund","year":"2013","unstructured":"Nordlund, J. et al. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biol. 14, r105 (2013).","journal-title":"Genome Biol."},{"key":"703_CR8","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature09727","volume":"471","author":"CG Mullighan","year":"2011","unstructured":"Mullighan, C. G. et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 471, 235\u2013239 (2011).","journal-title":"Nature"},{"key":"703_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4469","volume":"5","author":"BG Mar","year":"2014","unstructured":"Mar, B. G. et al. Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia. Nat. Commun. 5, 3469 (2014).","journal-title":"Nat. Commun."},{"key":"703_CR10","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1182\/blood-2009-04-214668","volume":"115","author":"L Milani","year":"2010","unstructured":"Milani, L. et al. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia. Blood 115, 1214\u20131225 (2010).","journal-title":"Blood"},{"key":"703_CR11","doi-asserted-by":"crossref","unstructured":"Hogan, L.E. et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood 118, 5218\u20135226 (2011).","DOI":"10.1182\/blood-2011-04-345595"},{"key":"703_CR12","doi-asserted-by":"crossref","unstructured":"Lee, S. T. et al. Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures. Nucleic Acids Res. 43, 2590\u20132602 (2015).","DOI":"10.1093\/nar\/gkv103"},{"key":"703_CR13","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.2217\/epi-2016-0052","volume":"8","author":"P Wahlberg","year":"2016","unstructured":"Wahlberg, P. et al. DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands. Epigenomics 8, 1367\u20131387 (2016).","journal-title":"Epigenomics"},{"key":"703_CR14","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/ng.3811","volume":"49","author":"G Jenkinson","year":"2017","unstructured":"Jenkinson, G., Pujadas, E., Goutsias, J. & Feinberg, A. P. Potential energy landscapes identify the information-theoretic nature of the epigenome. Nat. Genet. 49, 719\u2013729 (2017).","journal-title":"Nat. Genet."},{"key":"703_CR15","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12859-018-2086-5","volume":"19","author":"G Jenkinson","year":"2018","unstructured":"Jenkinson, G., Abante, J., Feinberg, A. P. & Goutsias, J. An information-theoretic approach to the modeling and analysis of whole-genome bisulfite sequencing data. BMC Bioinformatics 19, 87 (2018).","journal-title":"BMC Bioinformatics"},{"key":"703_CR16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12859-019-2777-6","volume":"20","author":"G Jenkinson","year":"2019","unstructured":"Jenkinson, G., Abante, J., Koldobskiy, M. A., Feinberg, A. P. & Goutsias, J. Ranking genomic features using an information-theoretic measure of epigenetic discordance. BMC Bioinformatics 20, 175 (2019).","journal-title":"BMC Bioinformatics"},{"key":"703_CR17","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1038\/ng.2442","volume":"44","author":"G Landan","year":"2012","unstructured":"Landan, G. et al. Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nat. Genet. 44, 1207\u20131214 (2012).","journal-title":"Nat. Genet."},{"key":"703_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/srep18037","volume":"5","author":"F Wang","year":"2015","unstructured":"Wang, F. et al. CellMethy: identification of a focal concordantly methylated pattern of CpGs revealed wide differences between normal and cancer tissues. Sci. Rep. 5, 18037 (2015).","journal-title":"Sci. Rep."},{"key":"703_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11790","volume":"7","author":"H Lilljebjorn","year":"2016","unstructured":"Lilljebjorn, H. et al. Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. Nat. Commun. 7, 11790 (2016).","journal-title":"Nat. Commun."},{"key":"703_CR20","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/ng.3691","volume":"48","author":"J Zhang","year":"2016","unstructured":"Zhang, J. et al. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nat. Genet. 48, 1481\u20131489 (2016).","journal-title":"Nat. Genet."},{"key":"703_CR21","doi-asserted-by":"crossref","unstructured":"Tsuzuki, S., Taguchi, O. & Seto, M. Promotion and maintenance of leukemia by ERG. Blood 117, 3858\u20133868 (2011).","DOI":"10.1182\/blood-2010-11-320515"},{"key":"703_CR22","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/nature07107","volume":"454","author":"A Meissner","year":"2008","unstructured":"Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766\u2013770 (2008).","journal-title":"Nature"},{"key":"703_CR23","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","volume":"518","author":"A Kundaje","year":"2015","unstructured":"Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317\u2013330 (2015).","journal-title":"Nature"},{"key":"703_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-102","volume":"12","author":"AA Sharov","year":"2011","unstructured":"Sharov, A. A. et al. Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity. BMC Genomics 12, 102 (2011).","journal-title":"BMC Genomics"},{"key":"703_CR25","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","volume":"28","author":"CY McLean","year":"2010","unstructured":"McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495\u2013501 (2010).","journal-title":"Nat. Biotechnol."},{"key":"703_CR26","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0165-4608(96)00172-0","volume":"92","author":"NA Heerema","year":"1996","unstructured":"Heerema, N. A. et al. Dicentric (9;20)(p11;q11) identified by fluorescence in situ hybridization in four pediatric acute lymphoblastic leukemia patients. Cancer Genet. Cytogenet. 92, 111\u2013115 (1996).","journal-title":"Cancer Genet. Cytogenet."},{"key":"703_CR27","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.3109\/10428194.2011.565436","volume":"52","author":"MS Felice","year":"2011","unstructured":"Felice, M. S. et al. Prognostic impact of t(1;19)\/TCF3\u2013PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin\u2013Frankfurt\u2013Munster-based protocols. Leuk. Lymphoma 52, 1215\u20131221 (2011).","journal-title":"Leuk. Lymphoma"},{"key":"703_CR28","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1200\/JCO.2010.30.7405","volume":"29","author":"CH Pui","year":"2011","unstructured":"Pui, C. H., Carroll, W. L., Meshinchi, S. & Arceci, R. J. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J. Clin. Oncol. 29, 551\u2013565 (2011).","journal-title":"J. Clin. Oncol."},{"key":"703_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/leu.2011.227","volume":"26","author":"D Bhojwani","year":"2012","unstructured":"Bhojwani, D. et al. ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy. Leukemia 26, 265\u2013270 (2012).","journal-title":"Leukemia"},{"key":"703_CR30","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/ng.3301","volume":"47","author":"K Paulsson","year":"2015","unstructured":"Paulsson, K. et al. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Nat. Genet. 47, 672\u2013676 (2015).","journal-title":"Nat. Genet."},{"key":"703_CR31","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41568-018-0015-6","volume":"18","author":"M Greaves","year":"2018","unstructured":"Greaves, M. A causal mechanism for childhood acute lymphoblastic leukaemia. Nat. Rev. Cancer 18, 471\u2013484 (2018).","journal-title":"Nat. Rev. Cancer"},{"key":"703_CR32","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1038\/leu.2012.332","volume":"27","author":"E De Braekeleer","year":"2013","unstructured":"De Braekeleer, E. et al. Acute lymphoblastic leukemia associated with RCSD1\u2013ABL1 novel fusion gene has a distinct gene expression profile from BCR\u2013ABL1 fusion. Leukemia 27, 1422\u20131424 (2013).","journal-title":"Leukemia"},{"key":"703_CR33","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/leu.2015.275","volume":"30","author":"S Goyama","year":"2016","unstructured":"Goyama, S. et al. UBASH3B\/Sts-1\u2013CBL axis regulates myeloid proliferation in human preleukemia induced by AML1\u2013ETO. Leukemia 30, 728\u2013739 (2016).","journal-title":"Leukemia"},{"key":"703_CR34","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.leukres.2012.05.009","volume":"36","author":"CM Wernicke","year":"2012","unstructured":"Wernicke, C. M. et al. MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival. Leuk. Res. 36, 1185\u20131192 (2012).","journal-title":"Leuk. Res."},{"key":"703_CR35","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.cancergen.2011.11.006","volume":"204","author":"R Zhang","year":"2011","unstructured":"Zhang, R. et al. A possible 5\u2032-NRIP1\/UHRF1-3\u2032 fusion gene detected by array CGH analysis in a Ph+ ALL patient. Cancer Genet. 204, 687\u2013691 (2011).","journal-title":"Cancer Genet."},{"key":"703_CR36","doi-asserted-by":"publisher","unstructured":"Sidhu, H. & Capalash, N. UHRF1: the key regulator of epigenetics and molecular target for cancer therapeutics. Tumour Biol. https:\/\/doi.org\/10.1177\/1010428317692205 (2017).","DOI":"10.1177\/1010428317692205"},{"key":"703_CR37","doi-asserted-by":"crossref","unstructured":"Ashraf, W. et al. The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer. Oncotarget 8, 51946\u201351962 (2017).","DOI":"10.18632\/oncotarget.17393"},{"key":"703_CR38","doi-asserted-by":"crossref","unstructured":"Chow, M. et al. Maintenance and pharmacologic targeting of ROR1 protein levels via UHRF1 in t(1;19) pre-B-ALL. Oncogene 37, 5221\u20135232 (2018).","DOI":"10.1038\/s41388-018-0299-8"},{"key":"703_CR39","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.molcel.2013.02.011","volume":"49","author":"JH Gibcus","year":"2013","unstructured":"Gibcus, J. H. & Dekker, J. The hierarchy of the 3D genome. Mol. Cell 49, 773\u2013782 (2013).","journal-title":"Mol. Cell"},{"key":"703_CR40","doi-asserted-by":"publisher","first-page":"e114","DOI":"10.1111\/pde.13408","volume":"35","author":"ML Chow","year":"2018","unstructured":"Chow, M. L., Kim, D., Kamath, S., Peng, D. & Luu, M. Use of antiviral medications in drug reaction with eosinophilia and systemic symptoms (DRESS): a case of infantile DRESS. Pediatr. Dermatol. 35, e114\u2013e116 (2018).","journal-title":"Pediatr. Dermatol."},{"key":"703_CR41","first-page":"183","volume":"26","author":"F Yan","year":"2011","unstructured":"Yan, F. et al. Inhibition effect of siRNA-downregulated UHRF1 on breast cancer growth. Cancer Biother. Radiopharm. 26, 183\u2013189 (2011).","journal-title":"Cancer Biother. Radiopharm."},{"key":"703_CR42","doi-asserted-by":"crossref","unstructured":"Yan, F., Wang, X., Shao, L., Ge, M. & Hu, X. Analysis of UHRF1 expression in human ovarian cancer tissues and its regulation in cancer cell growth. Tumour Biol. 36, 8887\u20138893 (2015).","DOI":"10.1007\/s13277-015-3638-1"},{"key":"703_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-016-0253-8","volume":"9","author":"TT Ge","year":"2016","unstructured":"Ge, T. T., Yang, M., Chen, Z., Lou, G. & Gu, T. UHRF1 gene silencing inhibits cell proliferation and promotes cell apoptosis in human cervical squamous cell carcinoma CaSki cells. J. Ovarian Res. 9, 42 (2016).","journal-title":"J. Ovarian Res."},{"key":"703_CR44","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1200\/JCO.2016.70.7836","volume":"35","author":"I Iacobucci","year":"2017","unstructured":"Iacobucci, I. & Mullighan, C. G. Genetic basis of acute lymphoblastic leukemia. J. Clin. Oncol. 35, 975\u2013983 (2017).","journal-title":"J. Clin. Oncol."},{"key":"703_CR45","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1182\/blood-2017-05-742643","volume":"130","author":"H Lilljebjorn","year":"2017","unstructured":"Lilljebjorn, H. & Fioretos, T. New oncogenic subtypes in pediatric B-cell precursor acute lymphoblastic leukemia. Blood 130, 1395\u20131401 (2017).","journal-title":"Blood"},{"key":"703_CR46","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.semcancer.2012.12.001","volume":"23","author":"KL Reddy","year":"2013","unstructured":"Reddy, K. L. & Feinberg, A. P. Higher order chromatin organization in cancer. Semin. Cancer Biol. 23, 109\u2013115 (2013).","journal-title":"Semin. Cancer Biol."},{"key":"703_CR47","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cell.2013.03.008","volume":"153","author":"H Shen","year":"2013","unstructured":"Shen, H. & Laird, P. W. Interplay between the cancer genome and epigenome. Cell 153, 38\u201355 (2013).","journal-title":"Cell"},{"key":"703_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0061-y","volume":"6","author":"W Timp","year":"2014","unstructured":"Timp, W. et al. Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors. Genome Med. 6, 61 (2014).","journal-title":"Genome Med."},{"key":"703_CR49","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/s43018-020-00131-2","volume":"1","author":"M Duran-Ferrer","year":"2020","unstructured":"Duran-Ferrer, M. et al. The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome. Nat. Cancer 1, 1066\u20131081 (2020).","journal-title":"Nat. Cancer"},{"key":"703_CR50","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.cell.2012.02.045","volume":"148","author":"E Pujadas","year":"2012","unstructured":"Pujadas, E. & Feinberg, A. P. Regulated noise in the epigenetic landscape of development and disease. Cell 148, 1123\u20131131 (2012).","journal-title":"Cell"},{"key":"703_CR51","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nrg.2016.13","volume":"17","author":"AP Feinberg","year":"2016","unstructured":"Feinberg, A. P., Koldobskiy, M. A. & Gondor, A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat. Rev. Genet. 17, 284\u2013299 (2016).","journal-title":"Nat. Rev. Genet."},{"key":"703_CR52","doi-asserted-by":"publisher","first-page":"705","DOI":"10.2217\/epi-2015-0017","volume":"8","author":"SC Zheng","year":"2016","unstructured":"Zheng, S. C., Widschwendter, M. & Teschendorff, A. E. Epigenetic drift, epigenetic clocks and cancer risk. Epigenomics 8, 705\u2013719 (2016).","journal-title":"Epigenomics"},{"key":"703_CR53","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.ccell.2014.10.012","volume":"26","author":"DA Landau","year":"2014","unstructured":"Landau, D. A. et al. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell 26, 813\u2013825 (2014).","journal-title":"Cancer Cell"},{"key":"703_CR54","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/nm.4125","volume":"22","author":"S Li","year":"2016","unstructured":"Li, S. et al. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat. Med. 22, 792\u2013799 (2016).","journal-title":"Nat. Med."},{"key":"703_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7921","volume":"6","author":"H Pan","year":"2015","unstructured":"Pan, H. et al. Epigenomic evolution in diffuse large B-cell lymphomas. Nat. Commun. 6, 6921 (2015).","journal-title":"Nat. Commun."},{"key":"703_CR56","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cels.2017.08.014","volume":"5","author":"TE Chan","year":"2017","unstructured":"Chan, T. E., Stumpf, M. P. H. & Babtie, A. C. Gene regulatory network inference from single-cell data using multivariate information measures. Cell Syst. 5, 251\u2013267.e3 (2017).","journal-title":"Cell Syst."},{"key":"703_CR57","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.18632\/oncotarget.26889","volume":"10","author":"H Giovinazzo","year":"2019","unstructured":"Giovinazzo, H. et al. A high-throughput screen of pharmacologically active compounds for inhibitors of UHRF1 reveals epigenetic activity of anthracycline derivative chemotherapeutic drugs. Oncotarget 10, 3040 (2019).","journal-title":"Oncotarget"},{"key":"703_CR58","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nature11305","volume":"488","author":"JL Lefebvre","year":"2012","unstructured":"Lefebvre, J. L., Kostadinov, D., Chen, W. V., Maniatis, T. & Sanes, J. R. Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature 488, 517\u2013521 (2012).","journal-title":"Nature"},{"key":"703_CR59","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.semcdb.2017.07.007","volume":"69","author":"N El Hajj","year":"2017","unstructured":"El Hajj, N., Dittrich, M. & Haaf, T. Epigenetic dysregulation of protocadherins in human disease. Semin. Cell Dev. Biol. 69, 172\u2013182 (2017).","journal-title":"Semin. Cell Dev. Biol."},{"key":"703_CR60","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.immuni.2008.05.015","volume":"29","author":"S Dias","year":"2008","unstructured":"Dias, S., Mansson, R., Gurbuxani, S., Sigvardsson, M. & Kee, B. L. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity 29, 217\u2013227 (2008).","journal-title":"Immunity"},{"key":"703_CR61","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1073\/pnas.0808866106","volume":"106","author":"CL Semerad","year":"2009","unstructured":"Semerad, C. L., Mercer, E. M., Inlay, M. A., Weissman, I. L. & Murre, C. E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors. Proc. Natl Acad. Sci. USA 106, 1930\u20131935 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"703_CR62","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1182\/blood.V77.4.687.687","volume":"77","author":"SP Hunger","year":"1991","unstructured":"Hunger, S. P. et al. The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. Blood 77, 687\u2013693 (1991).","journal-title":"Blood"},{"key":"703_CR63","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1126\/science.1386162","volume":"257","author":"T Inaba","year":"1992","unstructured":"Inaba, T. et al. Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science 257, 531\u2013534 (1992).","journal-title":"Science"},{"key":"703_CR64","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/biostatistics\/kxq005","volume":"11","author":"H Wu","year":"2010","unstructured":"Wu, H., Caffo, B., Jaffee, H. A., Irizarry, R. A. & Feinberg, A. P. Redefining CpG islands using hidden Markov models. Biostatistics 11, 499\u2013514 (2010).","journal-title":"Biostatistics"},{"key":"703_CR65","doi-asserted-by":"crossref","unstructured":"Ernst, J. & Kellis, M. Chromatin-state discovery and genome annotation with ChromHMM. Nat. Protoc. 12, 2478\u20132492 (2017).","DOI":"10.1038\/nprot.2017.124"},{"key":"703_CR66","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/nbt.3157","volume":"33","author":"J Ernst","year":"2015","unstructured":"Ernst, J. & Kellis, M. Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues. Nat. Biotechnol. 33, 364\u2013376 (2015).","journal-title":"Nat. Biotechnol."},{"key":"703_CR67","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","volume":"489","author":"Encode Project Consortium.","year":"2012","unstructured":"Encode Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57\u201374 (2012).","journal-title":"Nature"},{"key":"703_CR68","unstructured":"Press, W. H., Teukolsky, S. A., Vetterling, W. T. & Flannery, B. P. Numerical Recipes. The Art of Scientific Computing (Cambridge Univ. Press, 2007)."},{"key":"703_CR69","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1214\/aos\/1013699998","volume":"29","author":"Y Benjamini","year":"2001","unstructured":"Benjamini, Y. & Yekutieli, D. The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165\u20131188 (2001).","journal-title":"Ann. Stat."},{"key":"703_CR70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v023.i07","volume":"23","author":"DM Stasinopoulos","year":"2007","unstructured":"Stasinopoulos, D. M. & Rigby, R. A. Generalized additive models for location scale and shape (GAMLSS) in R. J. Stat. Softw. 23, 1\u201346 (2007).","journal-title":"J. Stat. Softw."},{"key":"703_CR71","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357\u2013360 (2015).","journal-title":"Nat. Methods"},{"key":"703_CR72","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","volume":"33","author":"M Pertea","year":"2015","unstructured":"Pertea, M. et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33, 290\u2013295 (2015).","journal-title":"Nat. Biotechnol."},{"key":"703_CR73","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"703_CR74","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. B"},{"key":"703_CR75","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/nmeth.2967","volume":"11","author":"PV Kharchenko","year":"2014","unstructured":"Kharchenko, P. V., Silberstein, L. & Scadden, D. T. Bayesian approach to single-cell differential expression analysis. Nat. Methods 11, 740\u2013742 (2014).","journal-title":"Nat. Methods"},{"key":"703_CR76","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.celrep.2015.12.089","volume":"14","author":"G Guo","year":"2016","unstructured":"Guo, G. et al. Serum-based culture conditions provoke gene expression variability in mouse embryonic stem cells as revealed by single-cell analysis. Cell Rep. 14, 956\u2013965 (2016).","journal-title":"Cell Rep."},{"key":"703_CR77","doi-asserted-by":"crossref","unstructured":"Jiao, Y., Widschwendter, M. & Teschendorff, A. E. A systems-level integrative framework for genome-wide DNA methylation and gene expression data identifies differential gene expression modules under epigenetic control. Bioinformatics 30, 2360\u20132366 (2014).","DOI":"10.1093\/bioinformatics\/btu316"},{"key":"703_CR78","doi-asserted-by":"crossref","unstructured":"Fisher, R. A Statistical Methods, Experimental Design, and Statistical Inference (Oxford Univ. Press, 1990).","DOI":"10.2307\/2532685"}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-021-00703-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-021-00703-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-021-00703-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T12:17:22Z","timestamp":1724847442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-021-00703-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":78,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["703"],"URL":"https:\/\/doi.org\/10.1038\/s41551-021-00703-2","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"31 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}