Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
received:
27
10
2020
accepted:
15
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
30
12
2021
Statut:
epublish
Résumé
Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.
Identifiants
pubmed: 34876579
doi: 10.1038/s41467-021-27326-0
pii: 10.1038/s41467-021-27326-0
pmc: PMC8651638
doi:
Substances chimiques
HLA-DP beta-Chains
0
HLA-DPB1 antigen
0
5-Aminolevulinate Synthetase
EC 2.3.1.37
ALAS2 protein, human
EC 2.3.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7104Subventions
Organisme : Wellcome Trust
ID : 205188/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008894/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/52/33808
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/12/12/29836
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/09/001/25945
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/14/6/31350
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/11/116/29288
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/4/34215
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/13/33281
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL136603
Pays : United States
Organisme : Medical Research Council
ID : MR/K020919/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/15/59/31839
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/18/10/33975
Pays : United Kingdom
Investigateurs
Marta Bleda
(M)
Charaka Hadinnapola
(C)
Matthias Haimel
(M)
Kate Auckland
(K)
Tobias Tilly
(T)
Jennifer M Martin
(JM)
Katherine Yates
(K)
Carmen M Treacy
(CM)
Margaret Day
(M)
Alan Greenhalgh
(A)
Debbie Shipley
(D)
Andrew J Peacock
(AJ)
Val Irvine
(V)
Fiona Kennedy
(F)
Shahin Moledina
(S)
Lynsay MacDonald
(L)
Eleni Tamvaki
(E)
Anabelle Barnes
(A)
Victoria Cookson
(V)
Latifa Chentouf
(L)
Souad Ali
(S)
Shokri Othman
(S)
Lavanya Ranganathan
(L)
J Simon R Gibbs
(JSR)
Rosa DaCosta
(R)
Joy Pinguel
(J)
Natalie Dormand
(N)
Alice Parker
(A)
Della Stokes
(D)
Dipa Ghedia
(D)
Yvonne Tan
(Y)
Tanaka Ngcozana
(T)
Ivy Wanjiku
(I)
Gary Polwarth
(G)
Rob V Mackenzie Ross
(RV)
Jay Suntharalingam
(J)
Mark Grover
(M)
Ali Kirby
(A)
Ali Grove
(A)
Katie White
(K)
Annette Seatter
(A)
Amanda Creaser-Myers
(A)
Sara Walker
(S)
Stephen Roney
(S)
Charles A Elliot
(CA)
Athanasios Charalampopoulos
(A)
Ian Sabroe
(I)
Abdul Hameed
(A)
Iain Armstrong
(I)
Neil Hamilton
(N)
Alex M K Rothman
(AMK)
Andrew J Swift
(AJ)
James M Wild
(JM)
Florent Soubrier
(F)
Mélanie Eyries
(M)
Marc Humbert
(M)
David Montani
(D)
Barbara Girerd
(B)
Laura Scelsi
(L)
Stefano Ghio
(S)
Henning Gall
(H)
Ardi Ghofrani
(A)
Harm J Bogaard
(HJ)
Anton Vonk Noordegraaf
(A)
Arjan C Houweling
(AC)
Anna Huis In't Veld
(AHI)
Gwen Schotte
(G)
Richard C Trembath
(RC)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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