Evidence map›Paper›PMID 41337937›Full record

ArticleEBioMedicine2025

Development and validation of a bronchoalveolar lavage genomic classifier for acute cellular rejection.

S Samuel Weigt, Jin Zhou, Tomoki Okuno, Megan L Neely, Shahrzad Lari, Vyacheslav Palchevskiy, Jamie L Todd, Laurie D Snyder, David Sayah, Michael Y Shino and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Observational
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

16 authors.

S Samuel WeigtDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: sweigt@mednet.ucla.edu.
Jin ZhouDepartment of Biostatistics, University of California, Los Angeles, CA, USA.
Tomoki OkunoDepartment of Biostatistics, University of California, Los Angeles, CA, USA.
Megan L NeelyDuke Clinical Research Institute, Durham, NC, USA.
Shahrzad LariDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Vyacheslav PalchevskiyDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Jamie L ToddDuke Clinical Research Institute, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
Laurie D SnyderDuke Clinical Research Institute, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
David SayahDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Michael Y ShinoDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
John ReynoldsDepartment of Medicine, Duke University, Durham, NC, USA.
Pali D ShahJohns Hopkins Medicine, Baltimore, MD, USA.
Lianne G SingerUniversity Health Network, University of Toronto, Toronto, Ontario, Canada.
Marie BudevCleveland Clinic, Cleveland, OH, USA.
Scott PalmerDuke Clinical Research Institute, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
John A BelperioDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Funding

The Lung Transplant Clinical Trials Network (LT-CTN)U01AI113315 · NIAID · DUKE UNIVERSITY · PI PALMER, SCOTT M · 2014 to 2018
$12.9M
NIAID NIH HHS U01 AI113315
6 · The paper itself

Abstract

backgroundAcute cellular rejection (ACR) is the main risk factor for chronic lung allograft dysfunction (CLAD), but diagnosis requires invasive transbronchial biopsy (TBB). We previously demonstrated the feasibility of bronchoalveolar lavage cell pellet (BAL-cp) gene expression for ACR diagnosis. We sought to develop and validate a genomic classifier for ACR in a multicenter cohort.

methodsWe performed RNA-seq on 806 BAL-cp from 181 lung transplant recipients enrolled in CTOT-20. Differential expression was based on fold difference >2.0 and False Discovery adjusted p-value <0.05. Samples were randomly split 80:20 into training and testing sets. A Random Forest model was optimized for area under the curve (AUC), and the threshold for genomic ACR was selected for classification accuracy. We validated performance in an independent single-centre cohort. Cox models evaluated risk for CLAD.

findingsFrom 37 clinically significant ACR and 151 stable control samples, we identified 62 ACR genes, indicating upregulation of T-cell receptor signalling, and downregulation of CTLA4 signalling in cytotoxic lymphocytes, among other enriched pathways. A 31-gene Random Forest model's AUC was 0.99 (SE 0.0053) in the training set, and 0.72 (SE 0.0874) in the test set. At a probability threshold of 0.396, accuracy for distinguishing clinically significant ACR cases from stable controls was 93.1% (specificity 95.4%, sensitivity 83.8%). In the independent validation cohort, accuracy was 82.1% (specificity 87.5%, sensitivity 73.3%). The model classified 138 (17.1%) CTOT-20 samples as genomic ACR. Late genomic ACR (≥90 days posttransplant) associated with increased CLAD risk (HR 2.52, 95% CI 1.47-4.34, p < 0.001).

interpretationA BAL-cp genomic classifier can identify ACR, predict CLAD risk, and may be a less invasive alternative to TBB after lung transplant.

fundingThis study was supported by the National Institute of Allergy and Infectious Diseases awards U01AI113315 and U01AI0635594, the Cystic Fibrosis Foundation award PALMER19AB0, and the Saul and Joyce Brandman Foundation Center for Lung Health at UCLA.

Indexed as

Bronchoalveolar Lavage FluidGenomicsGraft RejectionLung TransplantationAdultBiomarkersBronchoalveolar LavageFemaleGene Expression ProfilingHumansMaleMiddle AgedReproducibility of ResultsROC CurveBiomarkersAcute cellular rejectionChronic lung allograft dysfunctionGenomic classifierLung transplantationTranscriptomics

Identifiers

PMID41337937
PMCPMC12719680

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.