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

gene expression profiling multiomics pulmonary arterial hypertension

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
21 Aug 2024
Historique:
medline: 21 8 2024
pubmed: 21 8 2024
entrez: 21 8 2024
Statut: aheadofprint

Résumé

Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare. We 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. We identified 2 potentially protective gene network modules associated with vascular cells, and we validated Our integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.

Sections du résumé

BACKGROUND UNASSIGNED
Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.
METHODS UNASSIGNED
We 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.
RESULTS UNASSIGNED
We identified 2 potentially protective gene network modules associated with vascular cells, and we validated
CONCLUSIONS UNASSIGNED
Our integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.124.069864 PMID: 39167456
pubmed: 39167456
doi: 10.1161/CIRCULATIONAHA.124.069864
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Jason Hong (J)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).
ORCID: 0000-0002-5062-8926

Lejla Medzikovic (L)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).

Wasila Sun (W)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).
ORCID: 0009-0009-6419-5162

Brenda Wong (B)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).

Grégoire Ruffenach (G)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).
ORCID: 0000-0001-6419-4332

Christopher J Rhodes (CJ)

National Heart and Lung Institute, Imperial College London, UK (C.J.R., M.R.W.).
ORCID: 0000-0002-4962-3204

Adam Brownstein (A)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).
ORCID: 0009-0009-9900-2690

Lloyd L Liang (LL)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).
ORCID: 0009-0001-9999-9103

Laila Aryan (L)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).

Min Li (M)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).
ORCID: 0009-0002-8915-7145

Arjun Vadgama (A)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).
ORCID: 0009-0000-0124-7193

Zeyneb Kurt (Z)

Northumbria University, Newcastle Upon Tyne, UK (Z.K.).

Tae-Hwi Schwantes-An (TH)

Department 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 Mickler (EA)

Department of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).

Stefan Gräf (S)

Department of Medicine, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, UK (S.G., N.W.M.).
ORCID: 0000-0002-1315-8873

Mélanie Eyries (M)

Hôpital Pitié-Salpêtrière, AP-HP, Département de Génétique, Paris, France (M. Eyries).
ORCID: 0000-0003-1911-6698

Katie A Lutz (KA)

Department 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 Pauciulo (MW)

Department 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 Trembath (RC)

Department of Medical & Molecular Genetics, Faculty of Life Sciences & Medicine, King's College London, UK (R.C.T.).
ORCID: 0000-0003-0550-3400

Frédéric Perros (F)

CarMeN Laboratory, INSERM U1060, INRAE U1397, Université Claude Bernard Lyon 1, Pierre-Bénite, France (F.P.).
ORCID: 0000-0001-7730-2427

David Montani (D)

AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre, France (D.M.).
Université Paris-Saclay, Le Kremlin Bicêtre, France (D.M.).
UMR_S 999, Université Paris-Saclay, INSERM, Groupe Hospitalier Marie-Lannelongue-Saint Joseph, Le Plessis-Robinson, France (D.M.).
ORCID: 0000-0002-9358-6922

Nicholas W Morrell (NW)

Department of Medicine, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge, UK (S.G., N.W.M.).
ORCID: 0000-0001-5700-9792

Florent Soubrier (F)

UMR_S 1166, Sorbonne Université, INSERM, Paris, France (F.S.).
ORCID: 0000-0003-2571-7932

Martin R Wilkins (MR)

National Heart and Lung Institute, Imperial College London, UK (C.J.R., M.R.W.).
ORCID: 0000-0003-3926-1171

William C Nichols (WC)

Department 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 Aldred (MA)

Department 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 Desai (AA)

Department 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 Trégouët (DA)

Bordeaux Population Health Research Center, INSERM, Université Bordeaux, France (D.-A.T.).
ORCID: 0000-0001-9084-7800

Soban Umar (S)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).
ORCID: 0000-0001-8036-3079

Rajan Saggar (R)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).

Richard Channick (R)

Division of Pulmonary and Critical Care Medicine, University of California, Los Angeles. (J.H., B.W., A.B., L.L.L., A.V., R.S., R.C.).

Rubin M Tuder (RM)

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Aurora (R.M.T.).

Mark W Geraci (MW)

Department of Medicine, University of Pittsburgh, PA (M.W.G.).
ORCID: 0000-0002-2280-3424

Robert S Stearman (RS)

Department of Medicine, Indiana University, Indianapolis (T.-H.S.-A., E.A.M., M.A.A., A.A.D., R.S.S.).

Xia Yang (X)

Department of Integrative Biology and Physiology, University of California, Los Angeles. (X.Y.).
ORCID: 0000-0002-3971-038X

Mansoureh Eghbali (M)

Department of Anesthesiology & Perioperative Medicine, University of California, Los Angeles. (L.M., W.S., G.R., L.A., M.L., S.U., M. Eghbali).

Classifications MeSH