{"entity":{"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","aka":[],"tldr":"A method that reads whether a breast cancer still carries the oestrogen receptor from the DNA in a blood sample, when there is enough tumour DNA there.","summary":"Griffin profiles nucleosome protection and accessibility from cell-free DNA at as low as 0.1x whole-genome coverage, with a GC correction tailored to fragment size. It predicted oestrogen receptor subtype in 139 patients with metastatic breast cancer with at least 5 per cent detectable ctDNA, with an area under the curve of 0.89, and 0.96 in independent cohorts.","asOf":"2026-11-04","links":[{"label":"Doebley et al., Nat Commun 2022","url":"https://doi.org/10.1038/s41467-022-35076-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36463275/"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["diagnostics"],"technologies":["griffin-nucleosome-profiling","fragmentomics"],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2022,"doi":"10.1038/s41467-022-35076-w","pmid":"36463275","authors":"Doebley AL, Ko M, Liao H, et al.","paperType":"methods","findings":["ER subtype predicted with AUC 0.89 in 139 patients with at least 5% ctDNA.","AUC 0.96 in independent validation cohorts."],"whatItMeans":"The phenotype of advanced breast cancer, not only its mutations, can be read from blood. The method needs percent-level tumour DNA, so it does not yet reach residual disease after surgery.","caveats":["Metastatic disease, tumour fraction at least 5%.","In the full text, performance was lower between 5 and 10 per cent tumour fraction than above it."],"participants":139},"route":"/key-papers/paper-doebley-griffin-nucleosome-profiling-nat-commun-2022/","neighbours":{"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/"}],"technology":[{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/"},{"id":"griffin-nucleosome-profiling","kind":"technology","name":"Griffin (nucleosome profiling of cell-free DNA)","route":"/technologies/griffin-nucleosome-profiling/"}],"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/"}],"journal":[{"id":"nature-communications","kind":"journal","name":"Nature Communications","route":"/journals/nature-communications/"}],"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/"}]}}