{"entity":{"id":"griffin-nucleosome-profiling","kind":"technology","name":"Griffin (nucleosome profiling of cell-free DNA)","aka":["Griffin"],"tldr":"A way of reading which genes are switched on in a tumour from the pattern of where DNA in the blood is protected, used to tell whether a breast cancer still carries the oestrogen receptor.","summary":"Griffin (Doebley et al., Nature Communications 2022) profiles nucleosome protection and accessibility at transcription factor binding sites from cell-free DNA, with a GC correction tailored to fragment size, using whole-genome sequencing at coverage as low as 0.1x. It predicted oestrogen receptor subtype in 139 patients with metastatic breast cancer who had at least 5 per cent detectable ctDNA, with an area under the curve of 0.89, and 0.96 in independent cohorts. Performance depends on tumour fraction, so it reads the phenotype of advanced disease, not of residual disease at parts-per-million levels.","status":"emerging","asOf":"2026-11-04","links":[{"label":"Doebley et al., Nat Commun 2022 (Griffin)","url":"https://doi.org/10.1038/s41467-022-35076-w"}],"tags":[],"related":["meter-methylome-subtyping","epic-seq"],"cancers":["breast-hr-positive"],"sections":["diagnostics"],"technologies":["fragmentomics","liquid-biopsy"],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":["b-subclone-attribution-residual-disease"],"keyPapers":["paper-doebley-griffin-nucleosome-profiling-nat-commun-2022"],"journals":[],"dependsOn":[],"notes":[],"principle":"Where a transcription factor such as the oestrogen receptor is bound and active, the DNA is accessible and is cut differently when cells die; summing fragment coverage around thousands of its binding sites in plasma gives a readout of that factor's activity in the cells shedding DNA.","strengths":["Reads a phenotype (oestrogen receptor activity), not a mutation","Works from cheap low-coverage sequencing"],"limitations":["Validated only with at least 5 per cent tumour fraction","Tumour-naive: signal from tumour is diluted by the blood cells' own DNA"],"since":2022},"route":"/technologies/griffin-nucleosome-profiling/","neighbours":{"technology":[{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/"},{"id":"epic-seq","kind":"technology","name":"EPIC-seq (expression inference from cell-free DNA)","route":"/technologies/epic-seq/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"meter-methylome-subtyping","kind":"technology","name":"METER (methylome-based ctDNA detection and subtyping)","route":"/technologies/meter-methylome-subtyping/"},{"id":"plasma-epigenomic-profiling","kind":"technology","name":"Plasma epigenomic profiling (cfChIP-seq)","route":"/technologies/plasma-epigenomic-profiling/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"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-doebley-griffin-nucleosome-profiling-nat-commun-2022","kind":"paper","name":"A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA","route":"/key-papers/paper-doebley-griffin-nucleosome-profiling-nat-commun-2022/"}],"idea":[{"id":"idea-same-fragment-methylation-and-mutation","kind":"idea","name":"Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left","route":"/ideas/idea-same-fragment-methylation-and-mutation/"}]}}