Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease

Joshua Moss, Judith Magenheim, Daniel Neiman, Hai Zemmour, Netanel Loyfer, Amit Korach, Yaacov Samet, Myriam Maoz, Henrik Druid, Peter Arner, Keng-Yeh Fu, Endre Kiss, Kirsty L. Spalding, Giora Landesberg, Aviad Zick, Albert Grinshpun, A. M. James Shapiro, Markus Grompe, Avigail Dreazan Wittenberg, Benjamin Glaser, Ruth Shemer (), Tommy Kaplan () and Yuval Dor ()
Additional contact information
Joshua Moss: The Hebrew University-Hadassah Medical School
Judith Magenheim: The Hebrew University-Hadassah Medical School
Daniel Neiman: The Hebrew University-Hadassah Medical School
Hai Zemmour: The Hebrew University-Hadassah Medical School
Netanel Loyfer: The Hebrew University of Jerusalem
Amit Korach: Hadassah-Hebrew University Medical Center
Yaacov Samet: Hadassah-Hebrew University Medical Center
Myriam Maoz: Hadassah-Hebrew University Medical Center
Henrik Druid: Karolinska Institutet
Peter Arner: Karolinska Institutet
Keng-Yeh Fu: Karolinska Institutet
Endre Kiss: Karolinska Institutet
Kirsty L. Spalding: Karolinska Institutet
Giora Landesberg: Hadassah-Hebrew University Medical Center
Aviad Zick: Hadassah-Hebrew University Medical Center
Albert Grinshpun: Hadassah-Hebrew University Medical Center
A. M. James Shapiro: University of Alberta
Markus Grompe: Oregon Health & Science University
Avigail Dreazan Wittenberg: The Hebrew University-Hadassah Medical School
Benjamin Glaser: Hadassah-Hebrew University Medical Center
Ruth Shemer: The Hebrew University-Hadassah Medical School
Tommy Kaplan: The Hebrew University of Jerusalem
Yuval Dor: The Hebrew University-Hadassah Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07466-6

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DOI: 10.1038/s41467-018-07466-6

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