# ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin

Source: https://onco.cc/key-papers/paper-sadeh-cfchip-seq-nat-biotechnol-2021/  
OnCo record `paper-sadeh-cfchip-seq-nat-biotechnol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pulling down DNA in blood that was still wrapped in the marks of active genes showed which genes the cells it came from were using.

## Summary

Chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications, followed by sequencing (cfChIP-seq), was applied to 268 human samples. In healthy donors it identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to cell-free DNA; in liver disease it identified pathology-related changes in hepatocyte transcription; and in metastatic colorectal carcinoma it detected patient-specific information including transcriptionally active HER2 amplifications, at low sequencing depth.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: Nature Biotechnology
- Year: 2021
- DOI: 10.1038/s41587-020-00775-6
- Authors: Sadeh R, Sharkia I, Fialkoff G, et al.
- Findings: 268 samples profiled by cfChIP-seq.; Transcriptionally active HER2 amplifications detected in metastatic colorectal cancer.
- What it means: The first demonstration that gene activity in the tissue of origin can be read from nucleosomes in blood.
- Caveats: Metastatic disease for the cancer findings.

## Sources

- Sadeh et al., Nat Biotechnol 2021: https://doi.org/10.1038/s41587-020-00775-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33432199/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [Plasma epigenomic profiling (cfChIP-seq)](https://onco.cc/technologies/plasma-epigenomic-profiling/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/)
- journals: [Nature Biotechnology](https://onco.cc/journals/nature-biotechnology/)

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