Evidence map›Paper›PMID 39167456›Full record

ArticleCirculation2024

Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.

Jason Hong, Lejla Medzikovic, Wasila Sun, Brenda Wong, Grégoire Ruffenach, Christopher J Rhodes, Adam Brownstein, Lloyd L Liang, Laila Aryan, Min Li and 26 more

Erratum issuedAbstract read
In one paragraph

Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
–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

19 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. A Cross-Species and Sex-Specific Meta-Analysis of Transcriptomic Studies of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025
    Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

Jason Hong *Division of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.ORCID 0000-0002-5062-8926
Lejla Medzikovic *Departments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.
Wasila Sun *Departments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.ORCID 0009-0009-6419-5162
Brenda Wong *Division of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.
Grégoire RuffenachDepartments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.ORCID 0000-0001-6419-4332
Christopher J RhodesNational Heart and Lung Institute, Imperial College London, UK (C.J.R., M.R.W.).ORCID 0000-0002-4962-3204
Adam BrownsteinDivision of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.ORCID 0009-0009-9900-2690
Lloyd L LiangDivision of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.ORCID 0009-0001-9999-9103
Laila AryanDepartments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.
Min LiDepartments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.ORCID 0009-0002-8915-7145
Arjun VadgamaDivision of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.ORCID 0009-0000-0124-7193
Zeyneb KurtNorthumbria University, Newcastle Upon Tyne, UK (Z.K.).
Tae-Hwi Schwantes-AnDepartment of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).ORCID 0000-0001-6387-0095
Elizabeth A MicklerDepartment of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).
Stefan GräfDepartment of Medicine, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, UK (S.G., N.W.M.).ORCID 0000-0002-1315-8873
Mélanie EyriesHôpital Pitié-Salpêtrière, AP-HP, Département de Génétique, Paris, France (M. Eyries).ORCID 0000-0003-1911-6698
Katie A LutzDepartment of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, OH (K.A.L., M.W.P., W.C.N.).ORCID 0000-0002-9554-7679
Michael W PauciuloDepartment of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, OH (K.A.L., M.W.P., W.C.N.).ORCID 0000-0002-2141-2966
Richard C TrembathDepartment of Medical & Molecular Genetics, Faculty of Life Sciences & Medicine, King's College London, UK (R.C.T.).ORCID 0000-0003-0550-3400
Frédéric PerrosCarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon 1, Pierre-Bénite, France (F.P.).ORCID 0000-0001-7730-2427
David MontaniAP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre, France (D.M.).ORCID 0000-0002-9358-6922
Nicholas W MorrellDepartment of Medicine, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, UK (S.G., N.W.M.).ORCID 0000-0001-5700-9792
Florent SoubrierUMR_S 1166, Sorbonne Université, INSERM, Paris, France (F.S.).ORCID 0000-0003-2571-7932
Martin R WilkinsNational Heart and Lung Institute, Imperial College London, UK (C.J.R., M.R.W.).ORCID 0000-0003-3926-1171
William C NicholsDepartment of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, OH (K.A.L., M.W.P., W.C.N.).ORCID 0000-0003-1242-9237
Micheala A AldredDepartment of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).ORCID 0000-0002-7390-9181
Ankit A DesaiDepartment of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).ORCID 0000-0001-6427-616X
David-Alexandre TrégouëtBordeaux Population Health Research Center, INSERM, Université Bordeaux, France (D.-A.T.).ORCID 0000-0001-9084-7800
Soban UmarDepartments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.ORCID 0000-0001-8036-3079
Rajan SaggarDivision of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.
Richard ChannickDivision of Pulmonary and Critical Care Medicine (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.), University of California, Los Angeles.
Rubin M TuderDivision of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Aurora (R.M.T.).
Mark W GeraciDepartment of Medicine, University of Pittsburgh, PA (M.W.G.).ORCID 0000-0002-2280-3424
Robert S Stearman *Department of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).
Xia Yang *Integrative Biology and Physiology (X.Y.), University of California, Los Angeles.ORCID 0000-0002-3971-038X
Mansoureh Eghbali *Departments of Anesthesiology & Perioperative Medicine (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali), University of California, Los Angeles.ORCID 0000-0002-6252-9976

Funding

Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
National Biological Sample and Data Repository for PAHR24HL105333 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI NICHOLS, WILLIAM C · 2012 to 2016
$10.1M
Risk stratification in pulmonary arterial hypertension: Intersection of OMICs and longitudinal phenotypes through the PAH BiobankR01HL160941 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI DESAI, ANKIT A, NICHOLS, WILLIAM C · 2022 to 2025
$3.2M
Systems genetics approach to inflammatory mechanisms in atherosclerosisR01HL147883 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2019 to 2022
$3.0M
Role of intestinal inflammation in oxidized lipid induced pulmonary hypertensionR01HL162124 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EGHBALI, MANSOUREH, REDDY, SRINIVASA T. · 2022 to 2025
$2.4M
Role of miR125 in pulmonary hypertension secondary to interstitial lung diseaseR01HL147586 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EGHBALI, MANSOUREH · 2020 to 2023
$1.9M
Investigating the molecular mechanisms of right ventricular failure in pulmonary hypertensionR01HL161038 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Soban Umar · 2022 to 2026
$1.9M
Role of Chromosome Y gene, Uty, in protecting against Pulmonary HypertensionR01HL159865 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EGHBALI, MANSOUREH · 2021 to 2024
$1.9M
Role of the Novel MicroRNA-125b in Pulmonary Hypertension Associated with Pulmonary FibrosisK08HL141995 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI UMAR, SOBAN · 2019 to 2023
$879k
Integrative Multiomics to Uncover Novel Genes and Networks in Pulmonary Arterial HypertensionK08HL169982 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jason Hong · 2023 to 2026
$706k
NHLBI NIH HHS K08 HL141995NHLBI NIH HHS K08 HL169982NHLBI NIH HHS R01 HL147586NHLBI NIH HHS R01 HL147883NHLBI NIH HHS R01 HL159865NHLBI NIH HHS R01 HL160941NHLBI NIH HHS R01 HL161038NHLBI NIH HHS R01 HL162124NHLBI NIH HHS R24 HL105333NHLBI NIH HHS R24 HL123767
6 · The paper itself

Abstract

backgroundIntegrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.

methodsWe leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.

resultsWe identified 2 potentially protective gene network modules associated with vascular cells, and we validated

conclusionsOur integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.

Indexed as

Extracellular Matrix ProteinsLungPulmonary Arterial HypertensionAnimalsFemaleGene Expression ProfilingGene Regulatory NetworksGenome-Wide Association StudyHumansMaleMiddle AgedMultiomicsMyocytes, Smooth MusclePulmonary ArteryRatsRats, Sprague-DawleyASPN protein, humanExtracellular Matrix ProteinsSmad2 ProteinSMAD2 protein, humanSmad3 ProteinSMAD3 protein, humangene expression profilingmultiomicspulmonary arterial hypertension

Identifiers

PMID39167456
PMCPMC11473243

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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.