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

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Affiliations

  • 1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, 9112001, Israel.
      Authors
    • Moss J 1, 2
    • Magenheim J 1
    • Neiman D 1
    • Zemmour H 1
    • Wittenberg AD 1
    • Shemer R 1
    • Dor Y 1
    (7 authors)
  • 2. School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.
      Authors
    • Moss J 1, 2
    • Loyfer N 2
    • Kaplan T 2
    (3 authors)
  • 3. Department of Cardio-Thoracic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, 9112001, Israel.
      Authors
    • Korach A 3
    (1 author)
  • 4. Department of Vascular Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, 9112001, Israel.
      Authors
    • Samet Y 4
    (1 author)
  • 5. Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, 9112001, Israel.
      Authors
    • Maoz M 5
    • Zick A 5
    • Grinshpun A 5
    (3 authors)
    • Show all (12)

Nature Communications, 29 Nov 2018, 9(1):5068
https://doi.org/10.1038/s41467-018-07466-6 PMID: 30498206 PMCID: PMC6265251

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
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This article is based on a previously available preprint.

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.

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Read article at publisher's site: https://doi.org/10.1038/s41467-018-07466-6

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    Funding 

    Funders who supported this work.

    NCI NIH HHS (1)

    • Grant ID: U01 CA210171

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    NIDDK NIH HHS (1)

    • Grant ID: UC4 DK104216

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    Novo Nordisk Fonden (1)

    • Grant ID: NNF12OC1016064

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