{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:15:39Z","timestamp":1791501339823,"version":"4.3.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["817811"],"award-info":[{"award-number":["817811"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["771\/21"],"award-info":[{"award-number":["771\/21"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NHGRI","award":["R01HG009190"],"award-info":[{"award-number":["R01HG009190"]}]},{"name":"Israeli German R&D Nanotechnology","award":["13GW0282B"],"award-info":[{"award-number":["13GW0282B"]}]},{"name":"Israeli German R&D Nanotechnology","award":["NATI 61976"],"award-info":[{"award-number":["NATI 61976"]}]},{"name":"NIH NIGMS","award":["GM112966"],"award-info":[{"award-number":["GM112966"]}]},{"name":"NIH NIGMS","award":["1R01GM101396"],"award-info":[{"award-number":["1R01GM101396"]}]},{"name":"Salk Innovation"},{"DOI":"10.13039\/100001447","name":"Rita Allen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hearst Foundation"},{"name":"Paul F. Glenn Center for Biology of Aging Research at the Salk Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>DNA methylation, specifically, methylation of cytosine (C) nucleotides at the 5-carbon position (5-mC), is the most studied and significant epigenetic modification. Here we developed a chemoenzymatic procedure to fluorescently label non-methylated cytosines in CpG context, allowing epigenetic profiling of single DNA molecules spanning hundreds of thousands of base pairs. We used a CpG methyltransferase with a synthetic S-adenosyl-l-methionine cofactor analog to transfer an azide to cytosines instead of the natural methyl group. A fluorophore was then clicked onto the DNA, reporting on the amount and position of non-methylated CpGs. We found that labeling efficiency was increased up to 2-fold by the addition of a nucleosidase, presumably by degrading the inactive by-product of the cofactor after labeling, preventing its inhibitory effect. We used the method to determine the decline in global DNA methylation in a chronic lymphocytic leukemia patient and then performed whole-genome methylation mapping of the model plant Arabidopsis thaliana. Our genome maps show high concordance with published bisulfite sequencing methylation maps. Although mapping resolution is limited by optical detection to 500\u20131000 bp, the labeled DNA molecules produced by this approach are hundreds of thousands of base pairs long, allowing access to long repetitive and structurally variable genomic regions.<\/jats:p>","DOI":"10.1093\/nar\/gkac460","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T08:22:59Z","timestamp":1654244579000},"page":"e92-e92","source":"Crossref","is-referenced-by-count":31,"title":["Chemoenzymatic labeling of DNA methylation patterns for single-molecule epigenetic mapping"],"prefix":"10.1093","volume":"50","author":[{"given":"Tslil","family":"Gabrieli","sequence":"first","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Michaeli","sequence":"additional","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Avraham","sequence":"additional","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Torchinsky","sequence":"additional","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sapir","family":"Margalit","sequence":"additional","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, RWTH Aachen University , D-52056 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matyas","family":"Juhasz","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, RWTH Aachen University , D-52056 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceyda","family":"Coruh","sequence":"additional","affiliation":[{"name":"Plant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies , La Jolla , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissim","family":"Arbib","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Meir Hospital, Kfar Saba, Israel & Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui Sunny","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, and Barnett Institute of Chemical and Biological Analysis, Northeastern University , Boston , Massachusetts 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie\u00a0A","family":"Law","sequence":"additional","affiliation":[{"name":"Plant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies , La Jolla , CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmar","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, RWTH Aachen University , D-52056 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-7529","authenticated-orcid":false,"given":"Yuval","family":"Ebenstein","sequence":"additional","affiliation":[{"name":"School of Chemistry, Center for Nanoscience and Nanotechnology, Center for Light-Matter Interaction, The Center for Physics and Chemistry of Living Systems, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Tel Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"2022090900022218000_B1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/nar\/gkj461","article-title":"Microarray-based DNA methylation profiling: Technology and applications","volume":"34","author":"Schumacher","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2022090900022218000_B2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"2022090900022218000_B3","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1093\/nar\/10.8.2709","article-title":"Amount and distribution of 5-methylcytosine in human DNA from different types of tissues or cells","volume":"10","author":"Ehrlich","year":"1982","journal-title":"Nucleic Acids Res."},{"key":"2022090900022218000_B4","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.1038\/sj.onc.1205600","article-title":"CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future","volume":"21","author":"Esteller","year":"2002","journal-title":"Oncogene"},{"key":"2022090900022218000_B5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1201\/9781420045802.pt1","article-title":"DNA hypomethylation in cancer","volume":"1","author":"Molloy","year":"2008","journal-title":"Cancer Epigenet."},{"key":"2022090900022218000_B6","doi-asserted-by":"crossref","first-page":"5400","DOI":"10.1038\/sj.onc.1205651","article-title":"DNA methylation in cancer: Too much, but also too little","volume":"21","author":"Ehrlich","year":"2002","journal-title":"Oncogene"},{"key":"2022090900022218000_B7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cancergencyto.2004.04.004","article-title":"Global hypomethylation is common in prostate cancer cells: A quantitative predictor for clinical outcome","volume":"156","author":"Brothman","year":"2005","journal-title":"Cancer Genet. Cytogenet."},{"key":"2022090900022218000_B8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.yexmp.2006.08.002","article-title":"In situ detection of global DNA hypomethylation in exfoliative urine cytology of patients with suspected bladder cancer","volume":"82","author":"Seifert","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"2022090900022218000_B9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0021-9258(18)66148-4","article-title":"S-Adenosylmethionine; a new intermediate formed enzymatically from L-methionine and adenosinetriphosphate","volume":"204","author":"CATONI","year":"1953","journal-title":"J. Biol. Chem."},{"key":"2022090900022218000_B10","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41580-018-0016-z","article-title":"Dynamics and function of DNA methylation in plants","volume":"19","author":"Zhang","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022090900022218000_B11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature06745","article-title":"Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning","volume":"452","author":"Cokus","year":"2008","journal-title":"Nature"},{"key":"2022090900022218000_B12","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.cell.2008.03.029","article-title":"Highly integrated single-base resolution maps of the epigenome in Arabidopsis","volume":"133","author":"Lister","year":"2008","journal-title":"Cell"},{"key":"2022090900022218000_B13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jgg.2013.03.010","article-title":"An integrated workflow for DNA methylation analysis","volume":"40","author":"Li","year":"2013","journal-title":"J. Genet. Genomics"},{"key":"2022090900022218000_B14","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1126\/science.1240617","article-title":"Single-cell DNA-methylation analysis preimplantation embryos","volume":"341","author":"Lorthongpanich","year":"2013","journal-title":"Science"},{"key":"2022090900022218000_B15","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nbt.3598","article-title":"Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction","volume":"34","author":"Mooijman","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2022090900022218000_B16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nmeth.1779","article-title":"Sensitive and specific single-molecule sequencing of 5- hydroxymethylcytosine","volume":"9","author":"Song","year":"2012","journal-title":"Nat. Methods"},{"key":"2022090900022218000_B17","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nmeth.1459","article-title":"Direct detection of DNA methylation during single-molecule, real-time sequencing","volume":"7","author":"Flusberg","year":"2010","journal-title":"Nat. Methods"},{"key":"2022090900022218000_B18","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nmeth.4189","article-title":"Mapping DNA methylation with high-throughput nanopore sequencing","volume":"14","author":"Rand","year":"2017","journal-title":"Nat. Methods"},{"key":"2022090900022218000_B19","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nmeth.4184","article-title":"Detecting DNA cytosine methylation using nanopore sequencing","volume":"14","author":"Simpson","year":"2017","journal-title":"Nat. Methods"},{"key":"2022090900022218000_B20","article-title":"De novo identification of DNA modifications enabled by genome-guided nanopore signal processing","author":"Stoiber","year":"2017"},{"key":"2022090900022218000_B21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.tig.2018.05.008","article-title":"The Third Revolution in Sequencing Technology","volume":"34","author":"van\u00a0Dijk","year":"2018","journal-title":"Trends Genet."},{"key":"2022090900022218000_B22","doi-asserted-by":"crossref","first-page":"7148","DOI":"10.1021\/acsnano.8b03023","article-title":"Epigenetic optical mapping of 5-hydroxymethylcytosine in nanochannel arrays","volume":"12","author":"Gabrieli","year":"2018","journal-title":"ACS Nano"},{"key":"2022090900022218000_B23","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1101\/gr.240739.118","article-title":"Long-read single-molecule maps of the functional methylome","volume":"29","author":"Sharim","year":"2019","journal-title":"Genome Res."},{"key":"2022090900022218000_B24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1021\/nn4050694","article-title":"Toward single-molecule optical mapping of the epigenome","volume":"8","author":"Levy-Sakin","year":"2014","journal-title":"ACS Nano"},{"key":"2022090900022218000_B25","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/s41467-018-08148-z","article-title":"Multi-platform discovery of haplotype-resolved structural variation in human genomes","volume":"10","author":"Chaisson","year":"2019","journal-title":"Nat. Commun."},{"key":"2022090900022218000_B26","doi-asserted-by":"crossref","first-page":"I327","DOI":"10.1093\/bioinformatics\/btab306","article-title":"Long reads capture simultaneous enhancer\u2013promoter methylation status for cell-type deconvolution","volume":"37","author":"Margalit","year":"2021","journal-title":"Bioinformatics"},{"key":"2022090900022218000_B27","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0014-5793(92)81201-V","article-title":"Mode of action of the Spiroplasma CpG methylase M.SssI","volume":"313","author":"Renbaum","year":"1992","journal-title":"FEBS Lett."},{"key":"2022090900022218000_B28","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/nar\/18.5.1145","article-title":"Cloning, characterization, and expression in Escherichia coli of the gene coding for the CpG DNA methylase from Spiroplasma sp. strain MQ1(M Sssl)","volume":"18","author":"Renbaum","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"2022090900022218000_B29","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1038\/ncomms3190","article-title":"DNA unmethylome profiling by covalent capture of CpG sites","volume":"4","author":"Kriukiene","year":"2013","journal-title":"Nat. Commun."},{"key":"2022090900022218000_B30","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1021\/jm00254a016","article-title":"Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 1. Modification of the amino acid portion of S-adenosylhomocysteine","volume":"17","author":"Borchardt","year":"1974","journal-title":"J. Med. Chem."},{"key":"2022090900022218000_B31","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1021\/cb300669x","article-title":"Enhanced chemical stability of AdoMet analogues for improved methyltransferase-directed labeling of DNA","volume":"8","author":"Lukinavi\u010dius","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"2022090900022218000_B32","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S0003-2697(02)00267-1","article-title":"A stereospecific colorimetric assay for (S,S)-adenosylmethionine quantification based on thiopurine methyltransferase-catalyzed thiol methylation","volume":"308","author":"Cannon","year":"2002","journal-title":"Anal. Biochem."},{"key":"2022090900022218000_B33","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.1021\/ja908995p","article-title":"Enzyme-catalyzed transfer of a ketone group from an S-adenosylmethionine analogue: A tool for the functional analysis of methyltransferases","volume":"132","author":"Lee","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"2022090900022218000_B34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/ijc.32519","article-title":"5-Hydroxymethylcytosine as a clinical biomarker: fluorescence-based assay for high-throughput epigenetic quantification in human tissues","volume":"146","author":"Margalit","year":"2020","journal-title":"Int. J. Cancer"},{"key":"2022090900022218000_B35","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1080\/15592294.2019.1638700","article-title":"Global modulation in DNA epigenetics during pro-inflammatory macrophage activation","volume":"14","author":"Jain","year":"2019","journal-title":"Epigenetics"},{"key":"2022090900022218000_B36","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1093\/nar\/gkv904","article-title":"Sizing femtogram amounts of dsDNA by single-molecule counting","volume":"44","author":"Torchinsky","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2022090900022218000_B37","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/bioinformatics\/btx437","article-title":"Irys Extract","volume":"34","author":"Arielly","year":"2018","journal-title":"Bioinformatics"},{"key":"2022090900022218000_B38","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.cell.2016.06.044","article-title":"Epigenomic diversity in a global collection of Arabidopsis thaliana accessions","volume":"166","author":"Kawakatsu","year":"2016","journal-title":"Cell"},{"key":"2022090900022218000_B39","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41588-018-0115-y","article-title":"Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family","volume":"50","author":"Zhou","year":"2018","journal-title":"Nat. Genet."},{"key":"2022090900022218000_B40","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1093\/bioinformatics\/btt746","article-title":"TasiRNAdb: a database of ta-siRNA regulatory pathways","volume":"30","author":"Zhang","year":"2014","journal-title":"Bioinformatics"},{"key":"2022090900022218000_B41","doi-asserted-by":"crossref","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":"2022090900022218000_B42","doi-asserted-by":"crossref","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 Res."},{"key":"2022090900022218000_B43","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1002\/pro.524","article-title":"Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5\u2032-methylthioadenosine\/S-adenosylhomocysteine nucleosidase","volume":"19","author":"Ronning","year":"2010","journal-title":"Protein Sci."},{"key":"2022090900022218000_B44","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nrc3130","article-title":"A decade of exploring the cancer epigenome-biological and translational implications","volume":"11","author":"Baylin","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"2022090900022218000_B45","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1182\/blood.V80.8.2074.bloodjournal8082074","article-title":"Genomic hypomethylation in human chronic lymphocytic leukemia","volume":"80","author":"Wahlfors","year":"1992","journal-title":"Blood"},{"key":"2022090900022218000_B46","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nrg3683","article-title":"RNA-directed DNA methylation: an epigenetic pathway of increasing complexity","volume":"15","author":"Matzke","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"2022090900022218000_B47","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nature12178","article-title":"Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1","volume":"498","author":"Law","year":"2013","journal-title":"Nature"},{"key":"2022090900022218000_B48","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/nsr\/nwu003","article-title":"Non-coding RNAs and DNA methylation in plants","volume":"1","author":"Zhao","year":"2014","journal-title":"Natl. Sci. Rev."},{"key":"2022090900022218000_B49","doi-asserted-by":"crossref","first-page":"8599","DOI":"10.1039\/c3cc42543f","article-title":"Optical detection of epigenetic marks: sensitive quantification and direct imaging of individual hydroxymethylcytosine bases","volume":"49","author":"Michaeli","year":"2013","journal-title":"Chem. Commun."},{"key":"2022090900022218000_B50","doi-asserted-by":"crossref","first-page":"11414","DOI":"10.1039\/C9CC05198H","article-title":"Simultaneous detection of multiple DNA damage types by multi-colour fluorescent labelling","volume":"55","author":"Torchinsky","year":"2019","journal-title":"Chem. Commun."},{"key":"2022090900022218000_B51","doi-asserted-by":"crossref","first-page":"7771","DOI":"10.1021\/ja503677n","article-title":"Lighting up individual DNA damage sites by in vitro repair synthesis","volume":"136","author":"Zirkin","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"2022090900022218000_B52","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13148-017-0368-9","article-title":"Single-molecule quantification of 5-hydroxymethylcytosine for diagnosis of blood and colon cancers","volume":"9","author":"Gilat","year":"2017","journal-title":"Clin. Epigenet."},{"key":"2022090900022218000_B53","first-page":"S7","article-title":"DNA methylation changes in hematologic malignancies: Biologic and clinical implications","volume":"11","author":"Issa","year":"1997","journal-title":"Leukemia"},{"key":"2022090900022218000_B54","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.1038\/s41467-018-07271-1","article-title":"A chromosome-scale assembly of the sorghum genome using nanopore sequencing and optical mapping","volume":"9","author":"Deschamps","year":"2018","journal-title":"Nat. Commun."},{"key":"2022090900022218000_B55","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/tpj.13400","article-title":"Comprehensive definition of genome features in Spirodela polyrhiza by high-depth physical mapping and short-read DNA sequencing strategies","volume":"89","author":"Michael","year":"2017","journal-title":"Plant J."},{"key":"2022090900022218000_B56","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1101\/gr.213652.116","article-title":"Improving and correcting the contiguity of long-read genome assemblies of three plant species using optical mapping and chromosome conformation capture data","volume":"27","author":"Jiao","year":"2017","journal-title":"Genome Res."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/16\/e92\/45735669\/gkac460.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/16\/e92\/45735669\/gkac460.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T20:05:17Z","timestamp":1662667517000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/16\/e92\/6601286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":56,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,6,3]]},"published-print":{"date-parts":[[2022,9,9]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkac460","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.02.24.432628","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,9]]},"published":{"date-parts":[[2022,6,3]]}}}