{"entity":{"id":"genome-wide-ctdna-mutation-integration","kind":"technology","name":"Genome-wide ctDNA mutation integration (MRDetect, MRD-EDGE)","aka":["MRDetect","MRD-EDGE","Whole-genome ctDNA MRD"],"tldr":"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.","status":"emerging","asOf":"2026-11-04","links":[{"label":"Zviran et al., Nat Med 2020 (MRDetect)","url":"https://doi.org/10.1038/s41591-020-0915-3"},{"label":"Widman et al., Nat Med 2024 (MRD-EDGE)","url":"https://doi.org/10.1038/s41591-024-03040-4"}],"tags":[],"related":["accuscan-mrd"],"cancers":[],"sections":["diagnostics"],"technologies":["mrd-testing","wes-wgs"],"targets":[],"drugs":["truemrd"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","cfdna"],"trials":[],"people":[],"bottlenecks":["b-subclone-attribution-residual-disease"],"keyPapers":["paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020","paper-widman-mrd-edge-nat-med-2024"],"journals":[],"dependsOn":[],"notes":[],"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.","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"],"since":2020},"route":"/technologies/genome-wide-ctdna-mutation-integration/","neighbours":{"drug":[{"id":"accuscan-mrd","kind":"drug","name":"AccuScan","route":"/drugs/accuscan-mrd/"},{"id":"truemrd","kind":"drug","name":"TrueMRD","route":"/drugs/truemrd/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"term":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"bottleneck":[{"id":"b-subclone-attribution-residual-disease","kind":"bottleneck","name":"Naming which clone or phenotype is left after treatment","route":"/bottlenecks/b-subclone-attribution-residual-disease/"}],"paper":[{"id":"paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020","kind":"paper","name":"Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring","route":"/key-papers/paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020/"},{"id":"paper-widman-mrd-edge-nat-med-2024","kind":"paper","name":"Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment","route":"/key-papers/paper-widman-mrd-edge-nat-med-2024/"}]}}