GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE71378 Query DataSets for GSE71378
Status Public on Nov 04, 2015
Title Cell-free DNA comprises an in vivo, genome-wide nucleosome footprint that informs its tissue(s)-of-origin
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Nucleosomes are the basic unit of packaging of eukaryotic chromatin, and nucleosome positioning can differ substantially between cell types. Here, we sequence 14.5 billion plasma-borne cell-free DNA (cfDNA) fragments (700-fold coverage) to generate genome-wide maps of in vivo nucleosome occupancy. We identify 13 million local maxima of nucleosome protection, spanning 2.53 gigabases (Gb) of the human genome, whose positions and spacings correlate with nuclear architecture, gene structure and gene expression. We further show that short cfDNA fragments - poorly recovered by standard protocols - directly footprint the in vivo occupancy of DNA-bound transcription factors such as CTCF. The sequence composition of cfDNA has previously been used to noninvasively monitor cancer, pregnancy and organ transplantation, but a key limitation of this paradigm is its dependence on genotypic differences to distinguish between contributing tissues. We show that nucleosome spacing in gene bodies and cis-regulatory elements, inferred from cfDNA in healthy individuals, correlates most strongly with transcriptional and 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 in vivo nucleosome footprints can be used to infer the cell types that contribute to circulating cfDNA in pathological states such as cancer. Because it does not rely on genotypic differences, this strategy may enable the noninvasive cfDNA-based monitoring of a much broader set of clinical conditions than is currently possible.
Overall design Sequencing of cfDNA libraries from healthy individuals, pooled healthy individuals and individuals with disease for the identification of nucleosomes and protection from other DNA binding proteins.
Contributor(s) Shendure J
Citation(s) 26771485
Submission date Jul 27, 2015
Last update date May 15, 2019
Contact name Jay Shendure
Organization name University of Washington
Department Genome Sciences
Lab Shendure
Street address 3720 15th Ave NE
City Seattle
State/province WA
ZIP/Postal code 98195-5065
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (60)
GSM1833219 BH01
GSM1833220 IA01
GSM1833221 IA02
BioProject PRJNA291063
SRA SRP061633

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource 311.8 Mb (ftp)(http) BB 325.0 Mb (ftp)(http) BB 319.7 Mb (ftp)(http) BB 296.6 Mb (ftp)(http) BB 248.3 Mb (ftp)(http) BB
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap