# cfDNA fragmentomics

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

## TL;DR

Fragmentomics reads the sizes and positions of DNA fragments in blood, not the mutations. Cancer cells die messily and leave a recognisable fragmentation pattern.

## Summary

Fragmentomics analyses genome-wide cell-free DNA fragment length, end motifs, and nucleosome footprints at low sequencing depth, which is cheaper than deep mutation or methylation sequencing. DELFI Diagnostics commercialised FirstLook Lung (2023) as a blood test to increase uptake of low-dose CT screening, and presented the first randomised clinical-utility data (L301 FIRSTLUNG) at ATS 2026. Fragment features are also being layered into multi-cancer detection and MRD assays by Guardant, GRAIL, and academic groups.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-06
- Tags: frontier
- Principle: Plasma cfDNA is whole-genome sequenced at ~1-2x depth; machine learning on fragment-size distributions across genomic windows distinguishes tumour-derived from haematopoietic DNA.
- Strengths: Low cost per sample; Complements methylation and mutation signals; Sensitive to chromatin state of the cell of origin
- Limitations: Lower specificity than deep methylation panels alone; Tissue-of-origin resolution weaker than methylation; Clinical utility (mortality benefit) unproven

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cell-free_DNA
- DELFI FIRSTLUNG at ATS 2026: https://www.biospace.com/press-releases/delfi-diagnostics-to-present-first-clinical-utility-data-for-blood-based-lung-cancer-screening-at-ats-2026-international-conference

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Continuous and near-continuous ctDNA monitoring](https://onco.cc/technologies/continuous-ctdna-monitoring/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/)
- companies: [DELFI Diagnostics](https://onco.cc/companies/delfi-diagnostics/)
- bottlenecks: [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- ideas: [Push residual disease detection a hundredfold deeper with whole-genome methods](https://onco.cc/ideas/idea-bio2-whole-genome-mrd-depth/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Paths to cures: interception, eradication, control](https://onco.cc/roadmaps/cure-paths/)
- pathways: [Intravasation & circulating tumour cells](https://onco.cc/pathways/intravasation-ctc-survival/)

---
JSON: https://onco.cc/api/v1/entities/fragmentomics.json