ArticleeLife2023
Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 76 papers, 1 of them a synthesis 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.
K-ACCELERATE: A Multi-center Prospective Trial to Evaluate Clinical Utility of Multi Cancer Early Detection Test as a Triage Test for Symptomatic Participants
Multi-center Prospective Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer
Circulating Tumor DNA Mutations and Methylation Status as Biomarkers for Early Detection of Lung Cancer in Patients With Suspicious Lung Nodules
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multi-cancer early detection tests for general population screening: a systematic literature review.Health technology assessment (Winchester, England) · 2025Pooled it
- A streamlined hybrid-capture and genome-wide multi-omic platform for highly sensitive ctDNA minimal residual disease monitoring.The journal of liquid biopsy · 2026Article
- Circulating Cell-free DNA as a biomarker for radiation-induced injury: From mechanistic insights to clinical translation.Cancer metastasis reviews · 2026Review
- Liquid Biopsy for Molecular Residual Disease Detection and Postoperative Surveillance in Gastric Cancer: Current Evidence and Future Directions.International journal of molecular sciences · 2026Review
- NICE: A Two-Step Non-Invasive Framework for Embryo cfDNA Read Enrichment and Quality Assessment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multifeature sequencing-based liquid biopsy for cancer diagnosis and monitoring.Genome medicine · 2026Review
- Circulating Tumor DNA as a Biomarker of Treatment Response and Minimal Residual Disease in Diffuse Large B-Cell Lymphoma: A Literature Review.Journal of clinical medicine · 2026Review
- Cost-Effectiveness of Universal Low-Dose Computed Tomographic Lung Cancer Screening in Singapore.JAMA network open · 2026Article
- Organoid technology in cancer research.Molecular biomedicine · 2026Review
- TiSMeD: A tissue-specific methylation and expression database for biomarker and translational applications.Molecular therapy. Nucleic acids · 2026Article
- Frequency-Domain Transformation of cfDNA End-Motif Profiles Enhances Robust Cancer Detection.Genes · 2026Article
- Extracellular vesicle and particle biomarkers in cancer: a machine learning blueprint for liquid biopsy.Journal of nanobiotechnology · 2026Review
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- Expanding role of cell-free DNA for the early diagnosis and monitoring of pulmonary diseases.Chinese medical journal · 2026Review
- Artificial intelligence-powered liquid biopsy in cancer: a paradigm shift in cancer detection and personalized care.Cancer cell international · 2026Review
- Circulating Tumor DNA as a Biomarker in Pancreatic Cancer: Clinical Applications and Challenges.Clinical and translational gastroenterology · 2026Review
- Harnessing genomics for early cancer detection, risk stratification and prevention.Nature genetics · 2026Review
- Functional footprints of homologous recombination deficiency in prostate cancer revealed by ctDNA fragmentation and transcription factor accessibility.British journal of cancer · 2026Article
- Early Cancer Detection: What's Going on and What's Next.MedComm · 2026Review
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
65 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.
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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.