ArticlebioRxiv : the preprint server for biology2024
Circulating, cell-free methylated DNA indicates 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 readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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1 · What the graph read from itWhat it found
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2 · The registryThe trial behind it
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3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
12 authors.
Megan E McNamaraDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID 0000-0002-2591-0567 Sidharth S JainDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID 0000-0002-6263-651X 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 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.ORCID 0000-0002-3991-2766 Anna T RiegelDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID 0000-0001-6585-8612 Alexander H K KroemerMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA.
Anton WellsteinDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.ORCID 0000-0002-0570-4950 Funding
Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI MARCUS S NOEL · 1990 to 2026
$71.5MTRAINING 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
$2.6MUPIT: Unleash the Potential of Intestinal TransplantationR01AI132389 · NIAID · GEORGETOWN UNIVERSITY · PI KROEMER, ALEXANDER HELMUT KURT · 2017 to 2021
$2.4MDecoding the Tissue of Origin of Cellular Damage from Cell-free DNA in Liquid BiopsiesF30CA250307 · NCI · GEORGETOWN UNIVERSITY · PI BAREFOOT, MEGAN EVELYN · 2021 to 2025
$176kNCI NIH HHS F30 CA250307NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA231291NCI NIH HHS T32 CA009686NIAID NIH HHS R01 AI132389
6 · The paper itselfAbstract
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 patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. 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 beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention.
Identifiers
PMID38617373
PMCPMC11014558
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