ArticleProceedings of the National Academy of Sciences of the United States of America2023
Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 84 citations in OpenAlex.
- First-trimester non-invasive prediction of preterm birth using cell-free DNA fragmentomics.AJOG global reports · 2026Article
- Fragmentomic features of cell-free DNA in human spent blastocyst medium and their potential for non-invasive embryo ploidy assessment.Journal of assisted reproduction and genetics · 2026Article
- Circulating Cell-free DNA as a biomarker for radiation-induced injury: From mechanistic insights to clinical translation.Cancer metastasis reviews · 2026Review
- A cfDNA fragmentomics classifier for noninvasive differentiation of benign and malignant renal masses.Molecular biomedicine · 2026Article
- NICE: A Two-Step Non-Invasive Framework for Embryo cfDNA Read Enrichment and Quality Assessment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multidimensional 5-hydroxymethylcytosine features in cell-free DNA enable the detection, staging and subtyping of pancreatic ductal adenocarcinoma.Biomarker research · 2026Article
- Non-Invasive Diagnosis of Early Breast Cancer: Current and Emerging Liquid Biopsy Biomarkers.Cancers · 2026Review
- A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing.Science advances · 2026Article
- Early detection and subtyping of gastric cancer: A cell-free DNA fragmentome-based liquid biopsy method.iScience · 2026Article
- Cell-free DNA size deconvolution resolves nucleosomal origins and reveals tumor-associated fragmentomic alterations.Nature communications · 2026Article
- cfDECOR: a novel approach for estimating cell type contributions to cfDNA based on chromatin accessibility patterns.Scientific reports · 2026Article
- Longitudinal cell-free DNA methylome and fragmentome profiles in health uncover signatures of cell type and demographic origin.Genome medicine · 2026Article
- Holistic determination of ends of cfDNA molecules.Cell genomics · 2026Article
- Liquid biopsy epigenetics: establishing a molecular profile based on cell-free DNA.Molecular oncology · 2026Review
- Red Blood Cells Internalize Extracellular DNA via Apoptotic Bodies with Clinical Relevance to Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Machine learning-based cfDNA fragmentation profiling using automated capillary electrophoresis for early detection of hepatocellular carcinoma.Communications medicine · 2026Article
- cfGWAS reveal genetic basis of cell-free DNA end motifs.Nature communications · 2026Article
- Deep learning-based non-invasive profiling of tumor transcriptomes from cell-free DNA for precision oncology.bioRxiv : the preprint server for biology · 2026Article
- A pan-cancer compendium of 1,294 plasma cell-free DNA methylomes and fragmentomes enabling multicancer detection.Nature cancer · 2026Article
- Epigenetic profiling of circulating cell-free DNA for early detection and minimal residual disease assessment in lung cancer: a focus on DNA methylation.Frontiers in oncology · 2026Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.
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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.