ArticleNature biomedical engineering2021
Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.
Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05558436 (Comparison of Diagnostic Sensitivity Between Circulating Tumor DNA Methylation and Carcinoembryonic Antigen in Colorectal Cancer), which is not on this map. Cited by 108 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Comparison of Diagnostic Sensitivity Between Circulating Tumor DNA Methylation and Carcinoembryonic Antigen in Colorectal Cancer
Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- The effect of circulating tumor DNA on the prognosis of patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis.BMC cancer · 2024Pooled it
- Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer.BMC medicine · 2022Pooled it
- Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study.BMC medicine · 2021Trial
- Decoding coupled epigenetic-fragmentomic signals in circulating cell-free DNA for interpretable cancer diagnosis.Genome medicine · 2026Article
- Applications of circulating tumor DNA in unresectable and advanced non-small cell lung cancer immunotherapy: from stratification to therapeutic guidance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- High-Sensitivity ctDNA Analysis Uncovers Relevant Signals Missed by NGS in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Liquid biopsy: a new window on the BRCA genes.ESMO open · 2026Review
- Integrating structurally defined DNA-carbon nanotube sensors with machine learning for cancer detection.Science advances · 2026Article
- Liquid biopsy-based multi-omics approach for early detection of hepatocellular carcinoma (ASCEND-Hep): a multiphase prospective development and validation study.BMC medicine · 2026Article
- Review
- Artificial Intelligence in Oncology: A Comprehensive Cross-Cancer Translational Readiness Analysis Across 18 Malignancies.Cancers · 2026Review
- Current trends and future directions of artificial intelligence in lung cancer diagnosis.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Revolutionizing lung cancer screening: the rise of artificial intelligence integrating circulating tumor markers.World journal of surgical oncology · 2026Review
- Expanding role of cell-free DNA for the early diagnosis and monitoring of pulmonary diseases.Chinese medical journal · 2026Review
- Epigenetic Instability-Based Metrics in Cell-Free DNA for Early Cancer Detection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Explainable AI for Predicting Mortality Risk in Metastatic Cancer: Retrospective Cohort Study Using the Memorial Sloan Kettering-Metastatic Dataset.JMIR cancer · 2026Article
- Exploration of multi-omics liquid biopsy approaches for multi-cancer early detection: The PROMISE study.Innovation (Cambridge (Mass.)) · 2026Article
- Salivary cell-free DNA in head and neck cancer: emerging clinical applications and future perspectives.Oncology reviews · 2026Review
- Early detection of multiple cancers: the era of methylation-based liquid biopsy.Frontiers in oncology · 2026Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
31 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.