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Yee Foundation","award":["Development of Medical Genomics"],"award-info":[{"award-number":["Development of Medical Genomics"]}]},{"name":"Innovation and Technology Fund, Hong Kong SAR Government","award":["State Key Laboratory Programme"],"award-info":[{"award-number":["State Key Laboratory Programme"]}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","award":["Endowed Professorship"],"award-info":[{"award-number":["Endowed Professorship"]}],"id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,10,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA, we obtained a bird\u2019s eye view of the identities and contributions of these tissues to the circulating DNA pool. The tissue contributors and their relative proportions are identified by a bioinformatics deconvolution process that draws reference from DNA methylation signatures representative of each tissue type. We validated this approach in pregnant women, cancer patients, and transplant recipients. This method also allows one to identify the tissue of origin of genomic aberrations observed in plasma DNA. This approach has numerous research and diagnostic applications in prenatal testing, oncology, transplantation monitoring, and other fields.<\/jats:p>","DOI":"10.1073\/pnas.1508736112","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T23:08:42Z","timestamp":1442876922000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":709,"title":["Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments"],"prefix":"10.1073","volume":"112","author":[{"given":"Kun","family":"Sun","sequence":"first","affiliation":[{"name":"Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China;"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, 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, Shatin, New Territories, Hong Kong SAR, China;"},{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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Clin Chem 54, 482\u2013490 (2008).","journal-title":"Clin Chem"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1073\/pnas.0813371106","article-title":"Circulating microRNAs, potential biomarkers for drug-induced liver injury","volume":"106","author":"Wang K","year":"2009","unstructured":"K Wang, , Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 106, 4402\u20134407 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"e100360","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 P","year":"2014","unstructured":"P Jiang, , Methy-Pipe: An integrated bioinformatics pipeline for whole genome bisulfite sequencing data analysis. PLoS One 9, e100360 (2014).","journal-title":"PLoS One"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent WJ","year":"2002","unstructured":"WJ Kent, , The human genome browser at UCSC. Genome Res 12, 996\u20131006 (2002).","journal-title":"Genome Res"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/ng.298","article-title":"The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores","volume":"41","author":"Irizarry RA","year":"2009","unstructured":"RA Irizarry, , The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41, 178\u2013186 (2009).","journal-title":"Nat Genet"},{"key":"e_1_3_4_47_2","first-page":"1","article-title":"An R function for sampling linear inverse problems","volume":"30","author":"van den Meersche K","year":"2009","unstructured":"K van den Meersche, K Soetaert, D van Oevelen, An R function for sampling linear inverse problems. J Stat Softw 30, 1\u201315 (2009).","journal-title":"J Stat Softw"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"e21791","DOI":"10.1371\/journal.pone.0021791","article-title":"Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing","volume":"6","author":"Chen EZ","year":"2011","unstructured":"EZ Chen, , Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. 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