# 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; precision
- 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/), [GC Genome](https://onco.cc/companies/gc-genome/), [Gene Solutions](https://onco.cc/companies/gene-solutions/)
- 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/)
- key papers: [Clinical Validation of a Noninvasive Multi-Omics Method for Multicancer Early Detection in Retrospective and Prospective Cohorts](https://onco.cc/key-papers/paper-seekincare-j-mol-diagn-2025/), [Early detection of multiple cancer types using multidimensional cell-free DNA fragmentomics](https://onco.cc/key-papers/paper-bao-fragmentomics-nat-med-2025/), [Evaluation of cell-free DNA approaches for multi-cancer early detection](https://onco.cc/key-papers/paper-jamshidi-ccga1-cfdna-approaches-cancer-cell-2022/), [Genome-wide cell-free DNA fragmentation in patients with cancer](https://onco.cc/key-papers/paper-cristiano-delfi-fragmentomes-nature-2019/), [Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization](https://onco.cc/key-papers/paper-spot-mas-elife-2023/), [Prospective validation study: a non-invasive circulating tumor DNA-based assay for simultaneous early detection of multiple cancers in asymptomatic adults](https://onco.cc/key-papers/paper-spot-mas-k-detek-bmc-med-2025/)
- drugs: [ai-CANCERCH](https://onco.cc/drugs/ai-cancerch/), [CancerFind](https://onco.cc/drugs/cancerfind/), [SeekInCare](https://onco.cc/drugs/seekincare/), [SPOT-MAS](https://onco.cc/drugs/spot-mas/)
- trials: [INSPIRE (Singlera methylation and fragmentomics case-control study)](https://onco.cc/trials/inspire-singlera/), [PROFUTURE (methylation, fragmentation and protein test for five cancers)](https://onco.cc/trials/profuture-mced/)

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