TY  - JOUR
UR  - https://eprints.gla.ac.uk/260156/
ID  - enlighten260156
A1  - Kariotis, Sokratis
A1  - Jammeh, Emmanuel
A1  - Swietlik, Emilia M.
A1  - Pickworth, Josephine A.
A1  - Rhodes, Christopher J.
A1  - Otero, Pablo
A1  - Wharton, John
A1  - Iremonger, James
A1  - Dunning, Mark J.
A1  - Pandya, Divya
A1  - Mascarenhas, Thomas S.
A1  - Errington, Niamh
A1  - Thompson, A. A. Roger
A1  - Romanoski, Casey E.
A1  - Rischard, Franz
A1  - Garcia, Joe G. N.
A1  - Yuan, Jason X.-J.
A1  - An, Tae-Hwi Schwantes
A1  - Desai, Ankit A.
A1  - Coghlan, Gerry
A1  - Lordan, Jim
A1  - Corris, Paul A.
A1  - Howard, Luke S.
A1  - Condliffe, Robin
A1  - Kiely, David G.
A1  - Church, Colin
A1  - Pepke-Zaba, Joanna
A1  - Toshner, Mark
A1  - Wort, Stephen
A1  - Gräf, Stefan
A1  - Morrell, Nicholas W.
A1  - Wilkins, Martin R.
A1  - Lawrie, Allan
A1  - Wang, Dennis
A1  - Bleda, Marta
A1  - Hadinnapola, Charaka
A1  - Haimel, Matthias
A1  - Auckland, Kate
A1  - Tilly, Tobias
A1  - Martin, Jennifer M.
A1  - Yates, Katherine
A1  - Treacy, Carmen M.
A1  - Day, Margaret
A1  - Greenhalgh, Alan
A1  - Shipley, Debbie
A1  - Peacock, Andrew J.
A1  - Irvine, Val
A1  - Kennedy, Fiona
A1  - Moledina, Shahin
A1  - MacDonald, Lynsay
A1  - Tamvaki, Eleni
A1  - Barnes, Anabelle
A1  - Cookson, Victoria
A1  - Chentouf, Latifa
A1  - Ali, Souad
A1  - Othman, Shokri
A1  - Ranganathan, Lavanya
A1  - Gibbs, J. Simon R.
A1  - DaCosta, Rosa
A1  - Pinguel, Joy
A1  - Dormand, Natalie
A1  - Parker, Alice
A1  - Stokes, Della
A1  - Ghedia, Dipa
A1  - Tan, Yvonne
A1  - Ngcozana, Tanaka
A1  - Wanjiku, Ivy
A1  - Polwarth, Gary
A1  - Mackenzie Ross, Rob V.
A1  - Suntharalingam, Jay
A1  - Grover, Mark
A1  - Kirby, Ali
A1  - Grove, Ali
A1  - White, Katie
A1  - Seatter, Annette
A1  - Creaser-Myers, Amanda
A1  - Walker, Sara
A1  - Roney, Stephen
A1  - Elliot, Charles A.
A1  - Charalampopoulos, Athanasios
A1  - Sabroe, Ian
A1  - Hameed, Abdul
A1  - Armstrong, Iain
A1  - Hamilton, Neil
A1  - Rothman, Alex M. K.
A1  - Swift, Andrew J.
A1  - Wild, James M.
A1  - Soubrier, Florent
A1  - Eyries, Mélanie
A1  - Humbert, Marc
A1  - Montani, David
A1  - Girerd, Barbara
A1  - Scelsi, Laura
A1  - Ghio, Stefano
A1  - Gall, Henning
A1  - Ghofrani, Ardi
A1  - Bogaard, Harm J.
A1  - Noordegraaf, Anton Vonk
A1  - Houweling, Arjan C.
A1  - Veld, Anna Huis in?t
A1  - Schotte, Gwen
JF  - Nature Communications
TI  - Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood
PB  - Nature Research
VL  - 12
SN  - 2041-1723
Y1  - 2021/12/07/
AV  - public
N2  - 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.
ER  -