Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin
By M. Snyder, Martin Kircher, Andrew J. Hill, R. Daza, Jay Shendure. Cell, 2016
1,291 citations recorded by the source corpus.
Summary 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 indicate 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 differing cfDNA and cellular DNA genotypes, it may enable the noninvasive monitoring of a much broader set of clinical conditions than currently possible.
Subfields: Nephrology, Obstetrics and Gynecology, Surgery
View Paper: https://www.semanticscholar.org/paper/528d5aac22239deac333faec52bbf299dc6287dd
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In Obstetrics and Gynecology
Citations in the corpus
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