{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:46:02Z","timestamp":1781736362991,"version":"3.54.5"},"reference-count":41,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["Theme-based research scheme T12-403\/15-N"],"award-info":[{"award-number":["Theme-based research scheme T12-403\/15-N"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["Theme-based research scheme T12-401\/16-W"],"award-info":[{"award-number":["Theme-based research scheme T12-401\/16-W"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004853","name":"Chinese University of Hong Kong","doi-asserted-by":"publisher","award":["VCF2014021"],"award-info":[{"award-number":["VCF2014021"]}],"id":[{"id":"10.13039\/501100004853","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grail","award":["Collaborative research agreement"],"award-info":[{"award-number":["Collaborative research agreement"]}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring, and cancer screening.<\/jats:p>","DOI":"10.7554\/elife.64356","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T20:00:21Z","timestamp":1616443221000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.64356","source":"Crossref","is-referenced-by-count":29,"title":["Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology"],"prefix":"10.7554","volume":"10","author":[{"given":"Wanxia","family":"Gai","sequence":"first","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Zhou","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Agbor-Enoh","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, United States"},{"name":"Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, United States"},{"name":"Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-9030","authenticated-orcid":true,"given":"Xiaodan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Statistics, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Statistics, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Hang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Kyoo","family":"Jang","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, United States"},{"name":"Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Yang","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, United States"},{"name":"Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond HS","family":"Liang","sequence":"additional","affiliation":[{"name":"Comprehensive Oncology Centre, Hong Kong Sanatorium & Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Kong","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hong Kong Sanatorium & Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond SK","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hong Kong Sanatorium & Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Y","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossa WK","family":"Chiu","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Valantine","sequence":"additional","affiliation":[{"name":"Genomic Research Alliance for Transplantation (GRAfT), Bethesda, United States"},{"name":"Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-1691","authenticated-orcid":true,"given":"KC Allen","family":"Chan","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8746-0293","authenticated-orcid":true,"given":"YM Dennis","family":"Lo","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/pd.1700","article-title":"Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast","volume":"27","author":"Alberry","year":"2007","journal-title":"Prenatal Diagnosis"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets--update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Research"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"CCGA Consortium","year":"2020","journal-title":"Annals of Oncology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"18761","DOI":"10.1073\/pnas.1313995110","article-title":"Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing","volume":"110","author":"Chan","year":"2013","journal-title":"PNAS"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1373\/clinchem.2012.196014","article-title":"Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing","volume":"59","author":"Chan","year":"2013","journal-title":"Clinical Chemistry"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"E8159","DOI":"10.1073\/pnas.1615800113","article-title":"Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends","volume":"113","author":"Chan","year":"2016","journal-title":"PNAS"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1056\/NEJMoa1701717","article-title":"Analysis of plasma Epstein\u2013Barr Virus DNA to Screen for Nasopharyngeal Cancer","volume":"377","author":"Chan","year":"2017","journal-title":"New England Journal of Medicine"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"D794","DOI":"10.1093\/nar\/gkx1081","article-title":"The encyclopedia of DNA elements (ENCODE): data portal update","volume":"46","author":"Davis","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007803","article-title":"Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection","volume":"6","author":"De Vlaminck","year":"2014","journal-title":"Science Translational Medicine"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"13336","DOI":"10.1073\/pnas.1517494112","article-title":"Noninvasive monitoring of infection and rejection after lung transplantation","volume":"112","author":"De Vlaminck","year":"2015","journal-title":"PNAS"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/301089a0","article-title":"Hypomethylation distinguishes genes of some human cancers from their normal counterparts","volume":"301","author":"Feinberg","year":"1983","journal-title":"Nature"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1373\/clinchem.2018.290304","article-title":"Liver- and Colon-Specific DNA methylation markers in plasma for investigation of colorectal cancers with or without liver metastases","volume":"64","author":"Gai","year":"2018","journal-title":"Clinical Chemistry"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1126\/science.aac9593","article-title":"Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs","volume":"350","author":"Gasteiger","year":"2015","journal-title":"Science"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100360","article-title":"Methy-Pipe: an integrated bioinformatics pipeline for whole genome bisulfite sequencing data analysis","volume":"9","author":"Jiang","year":"2014","journal-title":"PLOS ONE"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"E10925","DOI":"10.1073\/pnas.1814616115","article-title":"Preferred end coordinates and somatic variants as signatures of circulating tumor DNA associated with hepatocellular carcinoma","volume":"115","author":"Jiang","year":"2018","journal-title":"PNAS"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1158\/2159-8290.CD-19-0622","article-title":"Plasma DNA End-Motif profiling as a fragmentomic marker in Cancer, pregnancy, and transplantation","volume":"10","author":"Jiang","year":"2020","journal-title":"Cancer Discovery"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1101\/gr.261396.120","article-title":"Detection and characterization of jagged ends of double-stranded DNA in plasma","volume":"30","author":"Jiang","year":"2020","journal-title":"Genome Research"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004323","article-title":"Noninvasive Whole-Genome sequencing of a human fetus","volume":"4","author":"Kitzman","year":"2012","journal-title":"Science Translational Medicine"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1097\/TP.0000000000002482","article-title":"Donor-specific Cell-free DNA as a biomarker in solid organ transplantation\u00a0A systematic review","volume":"103","author":"Knight","year":"2019","journal-title":"Transplantation"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"7361","DOI":"10.1073\/pnas.1405528111","article-title":"Noninvasive in vivo monitoring of tissue-specific global gene expression in humans","volume":"111","author":"Koh","year":"2014","journal-title":"PNAS"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004742","article-title":"Detection of chromosomal alterations in the circulation of Cancer patients with whole-genome sequencing","volume":"4","author":"Leary","year":"2012","journal-title":"Science Translational Medicine"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"E1826","DOI":"10.1073\/pnas.1519286113","article-title":"Identification of tissue-specific cell death using methylation patterns of circulating DNA","volume":"113","author":"Lehmann-Werman","year":"2016","journal-title":"PNAS"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9601","article-title":"Feasibility of blood testing combined with PET-CT to screen for Cancer and guide intervention","volume":"369","author":"Lennon","year":"2020","journal-title":"Science"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/s0140-6736(05)79055-3","article-title":"Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients","volume":"351","author":"Lo","year":"1998","journal-title":"The Lancet"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001720","article-title":"Maternal plasma DNA sequencing reveals the Genome-Wide genetic and mutational profile of the fetus","volume":"2","author":"Lo","year":"2010","journal-title":"Science Translational Medicine"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1373\/clinchem.2013.212274","article-title":"Noninvasive prenatal methylomic analysis by genomewide bisulfite sequencing of maternal plasma DNA","volume":"59","author":"Lun","year":"2013","journal-title":"Clinical Chemistry"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.3324\/haematol.2013.094243","article-title":"BLUEPRINT: mapping human blood cell epigenomes","volume":"98","author":"Martens","year":"2013","journal-title":"Haematologica"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1136\/jmg.2003.015784","article-title":"Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism","volume":"41","author":"Masuzaki","year":"2004","journal-title":"Journal of Medical Genetics"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Research"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or Platinum\u2013Pemetrexed in EGFR T790M\u2013Positive Lung Cancer","volume":"376","author":"Mok","year":"2017","journal-title":"New England Journal of Medicine"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-07466-6","article-title":"Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease","volume":"9","author":"Moss","year":"2018","journal-title":"Nature Communications"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes","volume":"518","author":"Roadmap Epigenomics Consortium","year":"2015","journal-title":"Nature"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002286","article-title":"Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: a prospective, observational, multicenter cohort study","volume":"14","author":"Sch\u00fctz","year":"2017","journal-title":"PLOS Medicine"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cell.2015.11.050","article-title":"Cell-free DNA comprises an in vivo nucleosome footprint that informs its Tissues-Of-Origin","volume":"164","author":"Snyder","year":"2016","journal-title":"Cell"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"E5503","DOI":"10.1073\/pnas.1508736112","article-title":"Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, Cancer, and transplantation assessments","volume":"112","author":"Sun","year":"2015","journal-title":"PNAS"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1101\/gr.242719.118","article-title":"Orientation-aware plasma cell-free DNA fragmentation analysis in open chromatin regions informs tissue of origin","volume":"29","author":"Sun","year":"2019","journal-title":"Genome Research"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1373\/clinchem.2014.221648","article-title":"Maternal plasma RNA sequencing for genome-wide transcriptomic profiling and identification of pregnancy-associated transcripts","volume":"60","author":"Tsui","year":"2014","journal-title":"Clinical Chemistry"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz8084","article-title":"ctDNA monitoring using patient-specific sequencing and integration of variant reads","volume":"12","author":"Wan","year":"2020","journal-title":"Science Translational Medicine"},{"key":"bib40","first-page":"71","article-title":"Detection of aberrant p16 methylation in the plasma and serum of liver Cancer patients","volume":"59","author":"Wong","year":"1999","journal-title":"Cancer Research"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1158\/1078-0432.CCR-08-2622","article-title":"Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung Cancer patients","volume":"15","author":"Yung","year":"2009","journal-title":"Clinical Cancer Research"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64356\/elife-64356-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64356\/elife-64356-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/64356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:06:20Z","timestamp":1697058380000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/64356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,23]]},"references-count":41,"alternative-id":["10.7554\/eLife.64356"],"URL":"https:\/\/doi.org\/10.7554\/elife.64356","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"accession","id":"EGAS00001004788","asserted-by":"subject"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.11.13.381178","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.64356.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.64356.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,23]]},"article-number":"e64356"}}