# EPIC-seq (expression inference from cell-free DNA)

Source: https://onco.cc/technologies/epic-seq/  
OnCo record `epic-seq` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A blood test method that infers which genes a tumour is using from how DNA fragments are cut at the start of each gene.

## Summary

EPIC-seq (Esfahani et al., Nature Biotechnology 2022) uses targeted sequencing of gene promoters and a feature called promoter fragmentation entropy to predict RNA expression at individual genes from cell-free DNA. 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 inferred expression profiles correlated with response to PD-1 or PD-L1 inhibitors. In the full text, lung cancer histology accuracy was 87 per cent at mean allele fractions above 5 per cent, 81 per cent between 1 and 5 per cent and 73 per cent below 1 per cent.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-11-04
- Also known as: EPIC-seq; Epigenetic expression inference from cell-free DNA-sequencing
- Principle: Active promoters lose a well-positioned nucleosome, so the sizes of fragments starting there are more varied; that variety (entropy) tracks how much the gene is expressed in the cells that shed the DNA.
- Since: 2022
- Strengths: Gene-level expression from blood; Targeted, so it is cheaper than whole-genome approaches
- Limitations: Accuracy falls with tumour fraction; Shown for lung cancer histology and lymphoma cell of origin, not for oestrogen receptor or TROP2

## Sources

- Esfahani et al., Nat Biotechnol 2022 (EPIC-seq): https://doi.org/10.1038/s41587-022-01222-4

## Connected records

- technologies: [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [Griffin (nucleosome profiling of cell-free DNA)](https://onco.cc/technologies/griffin-nucleosome-profiling/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Plasma epigenomic profiling (cfChIP-seq)](https://onco.cc/technologies/plasma-epigenomic-profiling/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/)
- bottlenecks: [Naming which clone or phenotype is left after treatment](https://onco.cc/bottlenecks/b-subclone-attribution-residual-disease/)
- key papers: [Inferring gene expression from cell-free DNA fragmentation profiles](https://onco.cc/key-papers/paper-esfahani-epic-seq-nat-biotechnol-2022/)

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