Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin

Details

• Alternative Title:
  Cell
• Personal Author:
  Snyder, Matthew W. ; Kircher, Martin ; Hill, Andrew J. ; Daza, Riza M. ; Shendure, Jay ; Snyder, Matthew W. ; Kircher, Martin ; Hill, Andrew J. ; Daza, Riza M. ; Shendure, Jay
• Description:
  Nucleosome positioning varies between cell types. By deep sequencing cell-free DNA (cfDNA), isolated from circulating blood plasma, we generated maps of genome-wide in vivo nucleosome occupancy and found that short cfDNA fragments harbor footprints of transcription factors. The cfDNA nucleosome occupancies correlate well with the nuclear architecture, gene structure, and expression observed in cells, suggesting that they could inform the cell type of origin. Nucleosome spacing inferred from cfDNA in healthy individuals correlates most strongly with epigenetic features of lymphoid and myeloid cells, consistent with hematopoietic cell death as the normal source of cfDNA. We build on this observation to show how nucleosome footprints can be used to infer cell types contributing to cfDNA in pathological states such as cancer. Since this strategy does not rely on genetic differences to distinguish between contributing tissues, it may enable the noninvasive monitoring of a much broader set of clinical conditions than currently possible.
• Subjects:
  Cell Line Chromatin Assembly And Disassembly DNA DNA Footprinting Genome, Human Genome-Wide Association Study Humans Neoplasms Nucleosomes Organ Specificity Repressor Proteins Sequence Analysis, DNA

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• Source:
  Cell. 164(0):57-68. ; Cell. 164(0):57-68.
• Pubmed ID:
  26771485
• Pubmed Central ID:
  PMC4715266
• Document Type:
  Journal Article
• Funding:
  DP1 HG007811/HG/NHGRI NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; 1DP1HG007811/DP/NCCDPHP CDC HHS/United States ; Howard Hughes Medical Institute/United States
• Volume:
  164
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:e26698e9fb32356ddfd9295c419c4c94b6dc668e4d796f9ebb4931cd028f302bdaabbf9303f01eb2c6cccd69bbab71b4b53cbdd382b5760040c97962faeeae4c
• Download URL:
  https://stacks.cdc.gov/view/cdc/39429/cdc_39429_DS1.pdf
• File Type:
  [PDF - 2.54 MB ]