Evidence map›Paper›PMID 40795850›Full record

ArticleCell genomics2025

The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance.

Kiki Cano-Gamez, Patrick Maclean, Masato Inoue, Sakineh Hussainy, Elisabeth Foss, Chloe Wainwright, Hanyu Qin, Stuart McKechnie, Chun-Xiao Song, Julian C Knight

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Article
  8. Metagenomic next-generation sequencing: new horizons in microbiology.Frontiers in cellular and infection microbiology · 2026
    Review
  9. Review
  10. Article
  11. Review
  12. 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 · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Kiki Cano-GamezCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK. Electronic address: k.e.cano-gamez@exeter.ac.uk.
Patrick MacleanCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Masato InoueLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sakineh HussainyLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Elisabeth FossCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Chloe WainwrightCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Hanyu QinCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.
Stuart McKechnieJohn Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Chun-Xiao SongLudwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Julian C KnightCentre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK; John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: julian.knight@well.ox.ac.uk.

Funding

Medical Research Council MR/V002503/1
6 · The paper itself

Abstract

Circulating cell-free DNA (cfDNA) is a promising molecular biomarker, but its role in severe infection is unclear. Here, we profile cfDNA from sepsis patients and controls, demonstrating a 41-fold increase during disease. Methylation-based deconvolution revealed similar cfDNA compositions in the two groups, suggesting that cfDNA accumulation during disease is due not to excess cell death but to impaired hepatic clearance. Fragmentation and end-motif patterns both support this hypothesis, suggesting prolonged exposure of cfDNA to circulating nucleases. In addition, we show that cfDNA retains nucleosome footprints informative of gene activity. By developing a novel method to quantify these footprints and integrate them with single-cell data, we report an increase in cfDNA from Kupffer cells and liver parenchyma in patients with liver dysfunction. Finally, we show that cfDNA contains pathogen-derived material, highlighting its diagnostic potential. This high-throughput, multimodal study provides a reference for understanding cfDNA's role in sepsis and critical illness.

Indexed as

Cell-Free Nucleic AcidsLiverSepsisAgedBiomarkersCase-Control StudiesDNA MethylationFemaleHumansKupffer CellsMaleMiddle AgedNucleosomesBiomarkersCell-Free Nucleic AcidsNucleosomescell-free DNAcritical illnessDNA methylationepigeneticsepigenomicsfragmentomicsinfectionliquid biopsiesmetagenomicssepsis

Identifiers

PMID40795850
PMCPMC12790999

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.