Evidence map›Paper›PMID 28624139›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2017

Applying rigor and reproducibility standards to assay donor-derived cell-free DNA as a non-invasive method for detection of acute rejection and graft injury after heart transplantation.

Sean Agbor-Enoh, Ilker Tunc, Iwijn De Vlaminck, Ulgen Fideli, Andrew Davis, Karen Cuttin, Kenneth Bhatti, Argit Marishta, Michael A Solomon, Annette Jackson and 10 more

2 registry-linked trialsOpen access · greenAbstract readComparative Study
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
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.

NCT03695601 active not recruitingnot on this mapstarted 2018, after this paper: background citation

Surveillance HeartCare® Outcomes Registry

TypeobservationalSponsorCareDxRan2018 to 2026Enrolled2,743ConditionsHeart Transplant RejectionArmsStandard of Care
NCT07647549 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Pulmonary Hypertension (PH) Biorepository for Translational Research

TypeobservationalSponsorNational Institutes of Health Clinical Center (CC)Ran2026 to 2036Enrolled1,000ConditionsPulmonary Hypertension
3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Molecular criteria for pulmonary antibody-mediated rejection are associated with an increased risk of allograft failure.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
    Observational
  4. Article
  5. Article
  6. Article
  7. Review
  8. %dd-cfDNA: The New Frontier for Heart/Lung Transplant Surveillance?Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  9. Review
  10. Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Organizing pneumonia is associated with molecular allograft injury and the development of antibody-mediated rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Liquid Biopsy, a Potential New Detection Method in Heart Allograft Rejection.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  20. 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

20 authors at 5 institutions in 1 country.

Sean Agbor-EnohDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Ilker TuncDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Iwijn De VlaminckDepartment of Bioengineering, Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
Ulgen FideliDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Andrew DavisDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Karen CuttinDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Kenneth BhattiDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Argit MarishtaDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Michael A SolomonDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Clinical Center, National Institutes of Health, Bethesda, Maryland.
Annette JacksonPulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Grace GraningerClinical Center, National Institutes of Health, Bethesda, Maryland.
Bonnie HarperClinical Center, National Institutes of Health, Bethesda, Maryland.
Helen LuikartDepartment of Medicine, Stanford University School of Medicine, Palo Alto, California.
Jennifer WylieDepartment of Medicine, Stanford University School of Medicine, Palo Alto, California.
Xujing WangDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Gerald BerryDepartment of Medicine, Stanford University School of Medicine, Palo Alto, California.
Charles MarboeDepartment of Medicine, New York Presbyterian University Hospital of Cornell and Columbia, New York, New York.
Kiran KhushDepartment of Medicine, New York Presbyterian University Hospital of Cornell and Columbia, New York, New York.
Jun ZhuDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Hannah ValantineDivision of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland; Laboratory of Transplantation Genomics, National Heart, Lung, and Blood Institute, Bethesda, Maryland. Electronic address: hannah.valantine@nih.gov.
National Heart Lung and Blood Institute · USCornell University · USStanford University · USJohns Hopkins University · USNational Institutes of Health Clinical Center · US

Funding

DNA Sequencing Core (DSC)ZICHL006058 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZHU, JUN · 2010 to 2016
$16.6M
Precision monitoring of kidney transplants via single-cell and single-molecule sequencingDP2AI138242 · NIAID · CORNELL UNIVERSITY · PI DE VLAMINCK, IWIJN · 2017 to 2017
$2.3M
RNA systems biologyZIAHL006230 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZHU, JUN · 2017 to 2018
$1.0M
Expression Profiling In Acute and Chronic Cardiac Allograft RejectionZIACL001171 · CLC · CLINICAL CENTER · PI SOLOMON, MICHAEL · 2009 to 2019
$0k
NIAID NIH HHS DP2 AI138242
6 · The paper itself

Abstract

backgroundUse of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts.

methodsAfter developing and validating the %ddcfDNA assay, we subjected the method to a rigorous test of its reproducibility. We measured %ddcfDNA in technical replicates performed by 2 independent laboratories and verified the reproducibility of %ddcfDNA patterns of 2 rejection phenotypes: acute cellular rejection and antibody-mediated rejection in distinct patient cohorts.

resultsWe observed strong concordance of technical-replicate %ddcfDNA measurements across 2 independent laboratories (slope = 1.02, R

conclusionsThe %ddcfDNA assay is precise and reproducible across laboratories and in samples from 2 distinct types of heart transplant rejection. These findings pave the way for larger studies to assess the clinical utility of %ddcfDNA as a marker of acute rejection after heart transplantation.

Indexed as

Tissue DonorsAcute DiseaseAdultBiomarkersCell-Free Nucleic AcidsFemaleGraft RejectionHeart TransplantationHumansLinear ModelsMalePrimary Graft DysfunctionReproducibility of ResultsStatistics, NonparametricBiomarkersCell-Free Nucleic Acidsallograft rejectionautomatedcell-free DNAheart transplantationreproducibility

Identifiers

PMID28624139
PMCPMC7988434
OpenAlexW2615183607

What OpenQuestion holds

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Registered trials

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.