# Push residual disease detection a hundredfold deeper with whole-genome methods

Source: https://onco.cc/ideas/idea-bio2-whole-genome-mrd-depth/  
OnCo record `idea-bio2-whole-genome-mrd-depth` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Current blood tests for leftover cancer track a few dozen mutations and miss low-level disease. Whole-genome and error-corrected methods integrate signal across thousands of tumour-specific sites plus methylation and fragment features, reaching detection near one part per million in research settings; cost, turnaround and reproducibility are the barriers.

## Summary

Whole-genome and error-corrected duplex approaches integrate signal across thousands to millions of tumour-specific sites, plus fragmentomic and methylation features, reaching detection limits reported near one part per million in research settings. Cost, turnaround and bioinformatics reproducibility are the barriers, not biology. If the limit of detection falls by two orders of magnitude, ctDNA-negative results become genuinely informative.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Genome-wide MRD detection lowers the limit of detection by at least fiftyfold versus fixed panels, raising sensitivity for relapse at the six-month landmark above 90% while keeping specificity above 99%.
- Rationale: Signal integration across many loci is a statistical rather than chemical improvement, so it scales with sequencing cost, which continues to fall. The same logic transformed non-invasive prenatal testing.
- Proposed test: Retrospective head-to-head on banked serial plasma from an adjuvant cohort with known outcomes, comparing panel and genome-wide assays on identical samples; then prospective validation within an MRD platform.
- Maturity: early-clinical
- Actor: data

## Sources

- Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022): https://doi.org/10.1056/NEJMoa2200075

## Connected records

- technologies: [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- companies: [DELFI Diagnostics](https://onco.cc/companies/delfi-diagnostics/), [Foresight Diagnostics](https://onco.cc/companies/foresight-diagnostics/), [Personalis (Tempus)](https://onco.cc/companies/personalis/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Variant allele frequency (VAF)](https://onco.cc/terms/vaf/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/)

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