# Cheap DNA fragment-pattern blood test as a first sieve before expensive cancer tests

Source: https://onco.cc/ideas/idea-prev-fragmentomics-first-tier/  
OnCo record `idea-prev-fragmentomics-first-tier` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

How DNA fragments in blood are chopped up differs in cancer and can be read with cheap, shallow sequencing. Used as a first sieve, it could cut the cost of population screening.

## Summary

The way DNA fragments in blood are chopped up differs in cancer and can be read with cheap, shallow sequencing, so this idea uses cell-free DNA fragmentomics as a first sieve, with deep methylation testing reserved for the top tenth by risk. DELFI Diagnostics and Johns Hopkins have validated fragmentomics with low-coverage whole-genome sequencing and machine learning in high-risk lung cohorts. Cost per test rather than accuracy limits yearly population screening, and tiering is how HPV and cytology triage already works. The test re-analyses banked plasma from a prospective MCED cohort with both assays, then runs a prospective tiered pilot. At early-clinical maturity it addresses the bottleneck The hardest cancers are found late.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: A two-tier design achieves at least 90% of the sensitivity of universal deep methylation testing at 30% or less of the sequencing cost.
- Rationale: Cost per test, not accuracy, limits yearly population screening; tiering is how HPV and cytology triage already works.
- Proposed test: Re-analyse banked plasma from a prospective MCED cohort with both assays; then run a prospective tiered pilot.
- Maturity: early-clinical
- Actor: industry

## Sources

- Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022): https://doi.org/10.1126/science.aay9040

## Connected records

- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- companies: [DELFI Diagnostics](https://onco.cc/companies/delfi-diagnostics/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- bottlenecks: [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- key papers: [Early detection of cancer](https://onco.cc/key-papers/paper-crosby-science/)

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