ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin
- 11 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 39 (5), 586-598
- https://doi.org/10.1038/s41587-020-00775-6
Abstract
Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.Keywords
This publication has 90 references indexed in Scilit:
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- Comprehensive Genome-wide Protein-DNA Interactions Detected at Single-Nucleotide ResolutionCell, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Histone modifications at human enhancers reflect global cell-type-specific gene expressionNature, 2009
- ChIP-seq accurately predicts tissue-specific activity of enhancersNature, 2009
- A Chromatin Landmark and Transcription Initiation at Most Promoters in Human CellsCell, 2007
- High-Resolution Profiling of Histone Methylations in the Human GenomeCell, 2007
- Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genomeNature Genetics, 2007