Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease.
Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease.
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DOI：
10.1038/s41467-018-07466-6
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发表时间：
2018-11-29
影响因子：
16.6
通讯作者：
Dor Y
中科院分区：
文献类型：
--
作者：
Moss J;Magenheim J;Neiman D;Zemmour H;Loyfer N;Korach A;Samet Y;Maoz M;Druid H;Arner P;Fu KY;Kiss E;Spalding KL;Landesberg G;Zick A;Grinshpun A;Shapiro AMJ;Grompe M;Wittenberg AD;Glaser B;Shemer R;Kaplan T;Dor Y
循环中无细胞DNA(CfDNA)的甲基化模式包含了体内最近发生的细胞死亡事件的丰富信息。在这里，我们提出了一种无偏见地确定cfDNA组织起源的方法，使用了25种人类组织和细胞类型的参考甲基化图谱。该方法在电子计算机模拟以及来自不同组织来源的已知比例的DNA体外混合中得到了验证。我们发现健康献血员血浆cfDNA来源于白细胞(55%)、红细胞祖细胞(30%)、血管内皮细胞(10%)和肝细胞(1%)。患者cfDNA的去卷积揭示了与败血症、胰岛移植、结肠癌、肺癌、乳腺癌和前列腺癌以及原发癌不明的临床结果相一致的组织贡献。我们提出了一种可以很容易地适应于在许多环境中研究cfDNA的细胞贡献者的程序，为了解健康和病理的人类组织动力学打开了一扇广阔的窗口。循环中无细胞DNA(CfDNA)的甲基化状态可以提供有关最近细胞死亡事件的信息。在这里，作者提出了一种方法来确定cfDNA的组织起源，使用了25种人类组织和细胞类型的参考甲基化图谱，并发现来自患者的cfDNA揭示了与临床结果一致的组织贡献。
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. The methylation status of circulating cell-free DNA (cfDNA) can be informative about recent cell death events. Here the authors present an approach to determine the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types, and find that cfDNA from patients reveals tissue contributions that agree with clinical findings.
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影响因子：
17.1
作者：
De Vlaminck I;Valantine HA;Snyder TM;Strehl C;Cohen G;Luikart H;Neff NF;Okamoto J;Bernstein D;Weisshaar D;Quake SR;Khush KK
通讯作者：
Khush KK
影响因子：
14.9
作者：
Li W;Li Q;Kang S;Same M;Zhou Y;Sun C;Liu CC;Matsuoka L;Sher L;Wong WH;Alber F;Zhou XJ
通讯作者：
Zhou XJ
严重败血症患者的预后效用和无细胞DNA的表征。
DOI：
10.1186/cc11466
发表时间：
2012-08-13
期刊：
Critical care (London, England)
影响因子：
--
作者：
Dwivedi DJ;Toltl LJ;Swystun LL;Pogue J;Liaw KL;Weitz JI;Cook DJ;Fox-Robichaud AE;Liaw PC;Canadian Critical Care Translational Biology Group
通讯作者：
Canadian Critical Care Translational Biology Group
影响因子：
29.4
作者：
Duncan AW;Hanlon Newell AE;Smith L;Wilson EM;Olson SB;Thayer MJ;Strom SC;Grompe M
通讯作者：
Grompe M
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C