ArticleScience translational medicine2021
Analysis of recurrently protected genomic regions in cell-free DNA found in urine.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 90 citations in OpenAlex.
- Advancing the applications of liquid biopsies in oncology.Nature reviews. Genetics · 2026Review
- Holistic determination of ends of cfDNA molecules.Cell genomics · 2026Article
- Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer.NPJ precision oncology · 2026Article
- Liquid biopsy epigenetics: establishing a molecular profile based on cell-free DNA.Molecular oncology · 2026Review
- Deep learning-based non-invasive profiling of tumor transcriptomes from cell-free DNA for precision oncology.bioRxiv : the preprint server for biology · 2026Article
- Comparative Analysis of Cell-Free DNA Fragmentation Patterns in Canines with Sarcoma and Tumor-Free Canines and Humans.Cancer research communications · 2026Article
- Unlocking the potential of urine-based liquid biopsy through improved reporting and standardization.Nature reviews. Cancer · 2026Article
- Impact of preanalytical variables on urinary cell-free DNA quality: Centrifugation, EDTA concentration, storage and thawing strategies.PloS one · 2026Article
- Variability and longitudinal dynamics of donor-derived cell-free DNA in kidney and liver recipients: a comparison of absolute and relative quantities in plasma and urine.Frontiers in transplantation · 2026Article
- The Clinical Utility of Cell-Free DNA in Brain Tumor Management: A Comprehensive Review.Journal of molecular neuroscience : MN · 2025Review
- The urinary eccDNA landscape in prostate cancer reveals associations with genome instability and vital roles in cancer progression.Journal of advanced research · 2025Article
- Evaluation of urinary cfDNA workflows for the molecular profiling of malignant disease.iScience · 2025Article
- Urine cf-nucleosomes: A non-invasive window into human physiology and disease.Cell genomics · 2025Article
- The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance.Cell genomics · 2025Article
- Circulating Cell-free DNA Fragmentomics Detection and Beyond.Aging and disease · 2025Review
- Donor-derived cell-free DNA-based liquid biopsies to determine future kidney transplant rejection.Kidney research and clinical practice · 2025Article
- Minimizing and quantifying uncertainty in AI-informed decisions: Applications in medicine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Early detection of multiple cancer types using multidimensional cell-free DNA fragmentomics.Nature medicine · 2025Article
- Evaluation of variability in cell-free DNA extraction efficiency from plasma and urine and spike-in normalization.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we characterized fragmentation patterns in urine cfDNA using whole-genome sequencing. Size distribution of urine cfDNA fragments showed multiple strong peaks between 40 and 120 base pairs (bp) with a modal size of 81- and sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were robust to preanalytical perturbations, such as at-home collection and delay in processing. Genome-wide sequencing coverage of urine cfDNA fragments revealed recurrently protected regions (RPRs) conserved across individuals, with partial overlap with nucleosome positioning maps inferred from plasma cfDNA. The ends of cfDNA fragments clustered upstream and downstream of RPRs, and nucleotide frequencies of fragment ends indicated enzymatic digestion of urine cfDNA. Compared to plasma, fragmentation patterns in urine cfDNA showed greater correlation with gene expression and chromatin accessibility in epithelial cells of the urinary tract. We determined that tumor-derived urine cfDNA exhibits a higher frequency of aberrant fragments that end within RPRs. By comparing the fraction of aberrant fragments and nucleotide frequencies of fragment ends, we identified urine samples from cancer patients with an area under the curve of 0.89. Our results revealed nonrandom genomic positioning of urine cfDNA fragments and suggested that analysis of fragmentation patterns across recurrently protected genomic loci may serve as a cancer diagnostic.
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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.