{"entity":{"id":"paper-esfahani-epic-seq-nat-biotechnol-2022","kind":"paper","name":"Inferring gene expression from cell-free DNA fragmentation profiles","aka":[],"tldr":"How DNA fragments in blood are cut at the start of each gene predicted how active that gene was, enough to tell lung and lymphoma subtypes apart.","summary":"Promoter fragmentation entropy is an epigenomic cell-free DNA feature that predicts RNA expression at individual genes. EPIC-seq applies it with targeted sequencing of promoters. In 329 blood samples from 201 patients with cancer and 87 healthy adults it classified subtypes of lung carcinoma and diffuse large B-cell lymphoma, and in serial samples from patients on PD-1 or PD-L1 inhibitors the inferred expression profiles correlated with clinical response.","asOf":"2026-11-04","links":[{"label":"Esfahani et al., Nat Biotechnol 2022","url":"https://doi.org/10.1038/s41587-022-01222-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35361996/"}],"tags":[],"related":[],"cancers":["nsclc","dlbcl"],"sections":["diagnostics"],"technologies":["epic-seq","fragmentomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2022,"doi":"10.1038/s41587-022-01222-4","pmid":"35361996","authors":"Esfahani MS, Hamilton EG, Mehrmohamadi M, et al.","paperType":"methods","findings":["329 samples from 201 patients with cancer and 87 healthy adults.","Lung carcinoma and DLBCL subtypes classified from blood.","Histology accuracy 87% above 5% mean allele fraction and 73% below 1% (full text)."],"whatItMeans":"Gene expression, not only mutation, can be inferred from blood, and the method keeps some accuracy below 1 per cent tumour DNA. That is still far above residual-disease levels.","caveats":["Accuracy falls with tumour fraction.","Not tested for oestrogen receptor or TROP2."],"participants":288},"route":"/key-papers/paper-esfahani-epic-seq-nat-biotechnol-2022/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"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/"}],"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-biotechnology","kind":"journal","name":"Nature Biotechnology","route":"/journals/nature-biotechnology/"}]}}