Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Sokratis Kariotis, Emmanuel Jammeh, Emilia M. Swietlik, Josephine A. Pickworth, Christopher J. Rhodes, Pablo Otero, John Wharton, James Iremonger, Mark J. Dunning, Divya Pandya, Thomas S. Mascarenhas, Niamh Errington, A. A. Roger Thompson, Casey E. Romanoski, Franz Rischard, Joe G. N. Garcia, Jason X.-J. Yuan, Tae-Hwi Schwantes An, Ankit A. Desai, Gerry Coghlan, Jim Lordan, Paul A. Corris, Luke S. Howard, Robin Condliffe, David G. Kiely, Colin Church, Joanna Pepke-Zaba, Mark Toshner, Stephen Wort, Stefan Gräf, Nicholas W. Morrell, Martin R. Wilkins, Allan Lawrie () and Dennis Wang ()
Additional contact information
Sokratis Kariotis: University of Sheffield
Emmanuel Jammeh: University of Sheffield
Emilia M. Swietlik: University of Cambridge
Josephine A. Pickworth: University of Sheffield
Christopher J. Rhodes: Imperial College London
Pablo Otero: Imperial College London
John Wharton: Imperial College London
James Iremonger: University of Sheffield
Mark J. Dunning: University of Sheffield
Divya Pandya: University of Cambridge
Thomas S. Mascarenhas: University of Sheffield
Niamh Errington: University of Sheffield
A. A. Roger Thompson: University of Sheffield
Casey E. Romanoski: University of Arizona
Franz Rischard: University of Arizona
Joe G. N. Garcia: University of Arizona
Jason X.-J. Yuan: University of California, San Diego
Tae-Hwi Schwantes An: Indiana University
Ankit A. Desai: Indiana University
Gerry Coghlan: University College London
Jim Lordan: Newcastle University
Paul A. Corris: Newcastle University
Luke S. Howard: Imperial College London
Robin Condliffe: University of Sheffield
David G. Kiely: University of Sheffield
Colin Church: University of Glasgow
Joanna Pepke-Zaba: Royal Papworth Hospital
Mark Toshner: University of Cambridge
Stephen Wort: Imperial College London
Stefan Gräf: University of Cambridge
Nicholas W. Morrell: University of Cambridge
Martin R. Wilkins: Imperial College London
Allan Lawrie: University of Sheffield
Dennis Wang: University of Sheffield

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27326-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27326-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27326-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().