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| Status |
Public on May 07, 2019 |
| Title |
Spatial co-fragmentation pattern of cell-free DNA recapitulates in vivo chromatin organization and identifies tissue-of-origin |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Three-dimensional chromatin organization varies across different cell types and is essential for gene regulation. However, current technologies are unable to assess in vivo genome-wide chromatin organization non-invasively. Here, we showed that long-range correlations in the fragment length of cell-free DNA (cfDNA) estimated from whole-genome sequencing recapitulate three-dimensional chromatin organization. The inferred organization is highly concordant with that measured by Hi-C in white blood cells from healthy donors, and is not explained by technical bias or sequence composition. Furthermore, the inferred organization reflects the differing genome organizations in the various cell types contributing to cfDNA, allowing quantification of cfDNA tissue-of-origin that is concordant with previous methods, but at much lower required DNA input. Our results, demonstrated in cfDNA from healthy individuals and cancer patients, may enable noninvasive monitoring of in vivo genome organization and accurate quantification of cell death in different clinical conditions.
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| Overall design |
Compare two-dimensional fragmentation pattern in cell free DNA with Hi-C at white blood cell and then deconvolute the signals to reference cell types
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| Contributor(s) |
Liu Y |
| Citation missing |
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| Submission date |
Jan 11, 2019 |
| Last update date |
May 10, 2019 |
| Contact name |
Yaping Liu |
| E-mail(s) |
lyping1986@gmail.com
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| Organization name |
Cincinnati Children's Hospital Medical Center
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| Department |
Department of Pediatrics
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| Lab |
EpiFluid Lab in Division of Human Genetics
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| Street address |
3333 Burnet Ave
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (2) |
| GPL20795 |
HiSeq X Ten (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA514727 |
| SRA |
SRP178527 |
