Evidence map›Paper›PMID 31600171›Full record

ArticleJCI insight2019

Transcriptional regulatory model of fibrosis progression in the human lung.

John E McDonough, Farida Ahangari, Qin Li, Siddhartha Jain, Stijn E Verleden, Jose Herazo-Maya, Milica Vukmirovic, Giuseppe DeIuliis, Argyrios Tzouvelekis, Naoya Tanabe and 18 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 2 pooled it
17.1field-weighted citation impact, top 1% 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.

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

116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 182 citations in OpenAlex.

  1. Pooled it
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  13. Monocyte-Derived LGMNResearch (Washington, D.C.) · 2026
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56 more citing papers are in PubMed but not listed here.

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

28 authors at 7 institutions in 4 countries.

John E McDonoughPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Farida AhangariPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Qin LiPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Siddhartha JainCarnegie Mellon University of Computer Science, Pittsburgh, Pennsylvania, USA.
Stijn E VerledenDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Jose Herazo-MayaPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Milica VukmirovicPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Giuseppe DeIuliisPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Argyrios TzouvelekisDivision of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
Naoya TanabeCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Fanny ChuCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Xiting YanPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Johny VerschakelenDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Robert J HomerDepartment of Pathology, Yale University School of Medicine, New Haven,Connecticut, USA.
Dimitris V ManatakisDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Junke ZhangDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jun DingCarnegie Mellon University of Computer Science, Pittsburgh, Pennsylvania, USA.
Karen MaesDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Laurens De SadeleerDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Robin VosDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Arne NeyrinckDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Panayiotis V BenosDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ziv Bar-JosephCarnegie Mellon University of Computer Science, Pittsburgh, Pennsylvania, USA.
Dean TantinDepartment of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
James C HoggCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada.
Bart M VanaudenaerdeDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Wim A WuytsDepartment of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Leuven Belgium.
Naftali KaminskiPulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Yale University · USKU Leuven · BECarnegie Mellon University · USUniversity of British Columbia · CAUniversity of Pittsburgh · USAlexander Fleming Biomedical Sciences Research Center · GRUniversity of Utah · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
TrainingU54HG008540 · NHGRI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAHAR, IVET, BERG, JEREMY M · 2014 to 2018
$12.8M
Genomic Analysis of Tissue and Cellular Heterogeneity in IPFR01HL127349 · NHLBI · YALE UNIVERSITY · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2015 to 2025
$5.9M
Role of Transcription Coactivator OCA-B in Gene Poising and Immunological MemoryR01AI100873 · NIAID · UNIVERSITY OF UTAH · PI TANTIN, DEAN · 2013 to 2022
$3.8M
Alveolar DevMAPU01HL122626 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMBALAVANAN, NAMASIVAYAM, HAGOOD, JAMES S. · 2014 to 2018
$3.7M
Epithelial Protective Effects of Thyroid Hormone Signaling in FibrosisR01HL141852 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$3.4M
Normal Aging Lung Cell Atlas (NALCA)U01HL145567 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$2.8M
Systems Level Causal Discovery in Heterogeneous TOPMed DataU01HL137159 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENOS, PANAGIOTIS V, SCIURBA, FRANK · 2017 to 2019
$1.8M
INTEGRATIVE GRAPHICAL MODELS FOR LARGE MULTI-MODAL BIOMEDICAL DATAR01LM012087 · NLM · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BENOS, PANAGIOTIS V, GLYMOUR, CLARK · 2015 to 2018
$1.3M
Deep and Integrative Analysis of RNA Sequencing Data to Identify Pathogenesis Heterogeneity of Chronic Lung DiseaseR21LM012884 · NLM · YALE UNIVERSITY · PI YAN, XITING · 2018 to 2019
$415k
NCATS NIH HHS UL1 TR001863NHGRI NIH HHS U54 HG008540NHLBI NIH HHS R01 HL127349NHLBI NIH HHS R01 HL141852NHLBI NIH HHS U01 HL122626NHLBI NIH HHS U01 HL137159NHLBI NIH HHS U01 HL145567NIAID NIH HHS R01 AI100873NLM NIH HHS R01 LM012087NLM NIH HHS R21 LM012884
6 · The paper itself

Abstract

To develop a systems biology model of fibrosis progression within the human lung we performed RNA sequencing and microRNA analysis on 95 samples obtained from 10 idiopathic pulmonary fibrosis (IPF) and 6 control lungs. Extent of fibrosis in each sample was assessed by microCT-measured alveolar surface density (ASD) and confirmed by histology. Regulatory gene expression networks were identified using linear mixed-effect models and dynamic regulatory events miner (DREM). Differential gene expression analysis identified a core set of genes increased or decreased before fibrosis was histologically evident that continued to change with advanced fibrosis. DREM generated a systems biology model (www.sb.cs.cmu.edu/IPFReg) that identified progressively divergent gene expression tracks with microRNAs and transcription factors that specifically regulate mild or advanced fibrosis. We confirmed model predictions by demonstrating that expression of POU2AF1, previously unassociated with lung fibrosis but proposed by the model as regulator, is increased in B lymphocytes in IPF lungs and that POU2AF1-knockout mice were protected from bleomycin-induced lung fibrosis. Our results reveal distinct regulation of gene expression changes in IPF tissue that remained structurally normal compared with moderate or advanced fibrosis and suggest distinct regulatory mechanisms for each stage.

Indexed as

Idiopathic Pulmonary FibrosisLungAgedAnimalsDisease ProgressionGene Expression RegulationHumansMaleMice, KnockoutMicroRNAsMiddle AgedModels, BiologicalTrans-ActivatorsTranscriptomeX-Ray MicrotomographyMicroRNAsPou2af1 protein, mouseTrans-ActivatorsFibrosisPulmonology

Identifiers

PMID31600171
PMCPMC6948862
OpenAlexW2979790944

What OpenQuestion holds

Textmetadata
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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.