Evidence map›Paper›PMID 40527875›Full record

ArticleNature communications2025

Circulating cell-free DNA methylation patterns indicate cellular sources of allograft injury after liver transplant.

Megan E McNamara, Sidharth S Jain, Kesha Oza, Vinona Muralidaran, Amber J Kiliti, A Patrick McDeed, Digvijay Patil, Yuki Cui, Marcel O Schmidt, Anna T Riegel and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Megan E McNamaraDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID http://orcid.org/0000-0002-2591-0567
Sidharth S JainDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Kesha OzaMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA.
Vinona MuralidaranMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA.
Amber J KilitiDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID http://orcid.org/0000-0002-8581-6222
A Patrick McDeedDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Digvijay PatilMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA.
Yuki CuiMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA.
Marcel O SchmidtDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Anna T RiegelDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Alexander KroemerMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA. alexander.kroemer@gunet.georgetown.edu.
Anton WellsteinDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. anton.wellstein@georgetown.edu.ORCID http://orcid.org/0000-0002-0570-4950

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Habtom W Ressom · 1990 to 2026
$71.5M
TRAINING GRANT IN TUMOR BIOLOGYT32CA009686 · NCI · GEORGETOWN UNIVERSITY · PI ANNA Tate RIEGEL, DAVID J ROBBINS · 1996 to 2026
$10.8M
(PQ #8) Biomarkers of efficacy and adverse events due to treatment with immune checkpoint inhibitorsR01CA231291 · NCI · GEORGETOWN UNIVERSITY · PI ATKINS, MICHAEL BENJAMIN, WELLSTEIN, ANTON · 2018 to 2022
$2.6M
UPIT: Unleash the Potential of Intestinal TransplantationR01AI132389 · NIAID · GEORGETOWN UNIVERSITY · PI KROEMER, ALEXANDER HELMUT KURT · 2017 to 2021
$2.4M
Decoding the Tissue of Origin of Cellular Damage from Cell-free DNA in Liquid BiopsiesF30CA250307 · NCI · GEORGETOWN UNIVERSITY · PI BAREFOOT, MEGAN EVELYN · 2021 to 2025
$176k
NCI NIH HHS F30 CA250307NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA231291NCI NIH HHS T32 CA009686NIAID NIH HHS R01 AI132389U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) F30-CA250307U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30-CA51008U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01-CA231291U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32-CA009686U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01-AI132389
6 · The paper itself

Abstract

Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to an atlas of cell-type-specific DNA methylation patterns derived from 476 methylomes of purified cells. For liver cell types, DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and functionally important regulatory regions. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA within the first month indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and intervention.

Indexed as

AllograftsCell-Free Nucleic AcidsDNA MethylationLiver TransplantationAdultAgedFemaleHepatocytesHumansLiverMaleMiddle AgedTransplantation, HomologousCell-Free Nucleic Acids

Identifiers

PMID40527875
PMCPMC12174327

What Socratic holds

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Registered trials

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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 Socratic graph.