ArticleProceedings of the National Academy of Sciences of the United States of America2016
Identification of tissue-specific cell death using methylation patterns of circulating DNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 367 papers.
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.
Study of DNA Methylation in Children and Adolescents With Type 1 Diabetes Mellitus
Pulmonary Hypertension (PH) Biorepository for Translational Research
Who cites it
367 citing papers in PubMed, 614 citations in OpenAlex.
- Trial
- Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.The Journal of clinical investigation · 2024Trial
- Validating quantitative PCR assays for cfDNA detection without DNA extraction in exercising SLE patients.Scientific reports · 2021Trial
- Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.Epigenetics · 2026Article
- Epigenetic Insights in Pediatric Multiple Sclerosis: DNA Methylation Highlights an Involvement of Epstein-Barr Virus Infection and Host Immune Networks.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Inferring tissue origin from cell-free DNA in metastatic cancer.Cancer metastasis reviews · 2026Review
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Liquid biopsy: current applications and future directions.Molecular biomedicine · 2026Review
- Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Population epigenetics: deciphering DNA methylation diversity and its implications for health, disease, and evolution.Molecular biology and evolution · 2026Review
- MethylSense: high accuracy machine learning-based diagnostics forJournal of clinical microbiology · 2026Article
- From DNA Methylation Microarray to Digital PCR: A Stepwise Strategy for Tissue Specific cfDNA Biomarker Development.Journal of clinical laboratory analysis · 2026Article
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- 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
- Longitudinal cell-free DNA methylome and fragmentome profiles in health uncover signatures of cell type and demographic origin.Genome medicine · 2026Article
- Detection of circulating tumor DNA in colorectal cancer patients using a methylation-specific droplet digital PCR multiplex.Molecular oncology · 2026Article
- Article
- Assessment of radiotherapy effect and toxicity using tissue-associated DNA methylation markers in cell-free DNA: a study on prostate cancer.Radiation and environmental biophysics · 2026Article
- Liquid biopsy epigenetics: establishing a molecular profile based on cell-free DNA.Molecular oncology · 2026Review
307 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
31 authors at 13 institutions in 6 countries.
Funding
Abstract
Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.
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What OpenQuestion holds
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.