{"entity":{"id":"plasma-epigenomic-profiling","kind":"technology","name":"Plasma epigenomic profiling (cfChIP-seq)","aka":["cfChIP-seq","ChIP-seq of plasma cell-free nucleosomes","Liquid biopsy epigenomic profiling"],"tldr":"Pulling down DNA in the blood that is still wrapped in the chemical marks of active genes, to see which genes the tumour has switched on, including the targets of some drugs.","summary":"Chromatin immunoprecipitation of cell-free nucleosomes carrying active histone marks (cfChIP-seq) was applied to 268 plasma samples by Sadeh and colleagues (Nature Biotechnology 2021), who detected transcriptionally active HER2 amplifications in metastatic colorectal cancer. Baca and colleagues (Nature Medicine 2023) extended it to histone modifications and DNA methylation from 1 mL of plasma, measuring 1,268 epigenomic profiles from 433 people with 15 cancers, and inferred the expression of diagnostic markers and drug targets and the activity of targetable transcription factors. In the full text, samples were analysed only above 3 per cent ctDNA (5 per cent for ERBB2), the level to which the tumour-fraction estimator is benchmarked, and the oestrogen receptor comparisons involved 17 to 19 patients. TROP2 (TACSTD2) is not among the genes reported.","status":"emerging","asOf":"2026-11-04","links":[{"label":"Sadeh et al., Nat Biotechnol 2021 (cfChIP-seq)","url":"https://doi.org/10.1038/s41587-020-00775-6"},{"label":"Baca et al., Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02605-z"}],"tags":[],"related":["epic-seq","griffin-nucleosome-profiling"],"cancers":[],"sections":["diagnostics"],"technologies":["liquid-biopsy","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":["b-subclone-attribution-residual-disease"],"keyPapers":["paper-sadeh-cfchip-seq-nat-biotechnol-2021","paper-baca-plasma-epigenomic-profiling-nat-med-2023"],"journals":[],"dependsOn":[],"notes":[],"principle":"Antibodies against marks of active promoters and enhancers (H3K4me3, H3K27ac) capture the nucleosomes that carried them in the dying cell; sequencing what is captured maps which genes were active in the cells shedding DNA.","strengths":["Reads transcriptional programmes and drug-target expression from blood","Works from 1 mL of plasma"],"limitations":["Proof of concept in advanced cancers at percent-level ctDNA","No TROP2 readout published","Small validation sets for oestrogen receptor"],"since":2021},"route":"/technologies/plasma-epigenomic-profiling/","neighbours":{"technology":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"epic-seq","kind":"technology","name":"EPIC-seq (expression inference from cell-free DNA)","route":"/technologies/epic-seq/"},{"id":"griffin-nucleosome-profiling","kind":"technology","name":"Griffin (nucleosome profiling of cell-free DNA)","route":"/technologies/griffin-nucleosome-profiling/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"term":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"bottleneck":[{"id":"b-subclone-attribution-residual-disease","kind":"bottleneck","name":"Naming which clone or phenotype is left after treatment","route":"/bottlenecks/b-subclone-attribution-residual-disease/"}],"paper":[{"id":"paper-sadeh-cfchip-seq-nat-biotechnol-2021","kind":"paper","name":"ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin","route":"/key-papers/paper-sadeh-cfchip-seq-nat-biotechnol-2021/"},{"id":"paper-baca-plasma-epigenomic-profiling-nat-med-2023","kind":"paper","name":"Liquid biopsy epigenomic profiling for cancer subtyping","route":"/key-papers/paper-baca-plasma-epigenomic-profiling-nat-med-2023/"}]}}