TY - JOUR
T1 - Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease
AU - Moss, Joshua
AU - Magenheim, Judith
AU - Neiman, Daniel
AU - Zemmour, Hai
AU - Loyfer, Netanel
AU - Korach, Amit
AU - Samet, Yaacov
AU - Maoz, Myriam
AU - Druid, Henrik
AU - Arner, Peter
AU - Fu, Keng Yeh
AU - Kiss, Endre
AU - Spalding, Kirsty L.
AU - Landesberg, Giora
AU - Zick, Aviad
AU - Grinshpun, Albert
AU - Shapiro, A. M.James
AU - Grompe, Markus
AU - Wittenberg, Avigail Dreazan
AU - Glaser, Benjamin
AU - Shemer, Ruth
AU - Kaplan, Tommy
AU - Dor, Yuval
N1 - Publisher Copyright: © 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85057566494&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-018-07466-6
DO - https://doi.org/10.1038/s41467-018-07466-6
M3 - مقالة
C2 - 30498206
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5068
ER -
