# Genome-wide ctDNA mutation integration (MRDetect, MRD-EDGE)

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

## TL;DR

Instead of reading a few of the tumour's mutations very deeply in blood, read the whole genome once and add up the faint signal from thousands of mutations.

## Summary

MRDetect (Zviran et al., Nature Medicine 2020) showed that deep sequencing of a small panel is limited by the number of DNA fragments in the tube, and that whole-genome sequencing of cell-free DNA, integrating the signal of thousands of somatic mutations, reached a tumour fraction detection sensitivity as low as 10^-5. MRD-EDGE (Widman et al., Nature Medicine 2024) added machine-learning error suppression that raised single-nucleotide-variant signal-to-noise about 300-fold, cut the aneuploidy needed for copy-number detection from 1 Gb to 200 Mb, detected ctDNA shed by precancerous colorectal adenomas, and allowed plasma-only monitoring without tumour tissue in melanoma and lung cancer on immunotherapy. The commercial descendant of the approach is TrueMRD; AccuScan is a related whole-genome method.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-11-04
- Also known as: MRDetect; MRD-EDGE; Whole-genome ctDNA MRD
- Principle: Plasma is sequenced across the whole genome at modest depth; each tumour mutation is seen at most once or twice, and the evidence is summed across thousands of sites, with a classifier separating real tumour fragments from sequencing errors.
- Since: 2020
- Strengths: Breadth replaces depth: thousands of sites rather than a few; No personalised panel to design
- Limitations: Each site is read about once, so the result is an aggregate tumour fraction and cannot say which clone is present; The parts-per-million results in MRD-EDGE come from in silico admixtures, not wet-laboratory dilutions

## Sources

- Zviran et al., Nat Med 2020 (MRDetect): https://doi.org/10.1038/s41591-020-0915-3
- Widman et al., Nat Med 2024 (MRD-EDGE): https://doi.org/10.1038/s41591-024-03040-4

## Connected records

- drugs: [AccuScan](https://onco.cc/drugs/accuscan-mrd/), [TrueMRD](https://onco.cc/drugs/truemrd/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- 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: [Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring](https://onco.cc/key-papers/paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020/), [Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment](https://onco.cc/key-papers/paper-widman-mrd-edge-nat-med-2024/)

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