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

Kariotis, S. et al. (2021) Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood. Nature Communications, 12, 7104. (doi: 10.1038/s41467-021-27326-0)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Church, Dr Colin and Peacock, Professor Andrew
• Authors: Kariotis, S., Jammeh, E., Swietlik, E. M., Pickworth, J. A., Rhodes, C. J., Otero, P., Wharton, J., Iremonger, J., Dunning, M. J., Pandya, D., Mascarenhas, T. S., Errington, N., Thompson, A. A. R., Romanoski, C. E., Rischard, F., Garcia, J. G. N., Yuan, J. X.-J., An, T.-H. S., Desai, A. A., Coghlan, G., Lordan, J., Corris, P. A., Howard, L. S., Condliffe, R., Kiely, D. G., Church, C., Pepke-Zaba, J., Toshner, M., Wort, S., Gräf, S., Morrell, N. W., Wilkins, M. R., Lawrie, A., Wang, D., Bleda, M., Hadinnapola, C., Haimel, M., Auckland, K., Tilly, T., Martin, J. M., Yates, K., Treacy, C. M., Day, M., Greenhalgh, A., Shipley, D., Peacock, A. J., Irvine, V., Kennedy, F., Moledina, S., MacDonald, L., Tamvaki, E., Barnes, A., Cookson, V., Chentouf, L., Ali, S., Othman, S., Ranganathan, L., Gibbs, J. S. R., DaCosta, R., Pinguel, J., Dormand, N., Parker, A., Stokes, D., Ghedia, D., Tan, Y., Ngcozana, T., Wanjiku, I., Polwarth, G., Mackenzie Ross, R. V., Suntharalingam, J., Grover, M., Kirby, A., Grove, A., White, K., Seatter, A., Creaser-Myers, A., Walker, S., Roney, S., Elliot, C. A., Charalampopoulos, A., Sabroe, I., Hameed, A., Armstrong, I., Hamilton, N., Rothman, A. M. K., Swift, A. J., Wild, J. M., Soubrier, F., Eyries, M., Humbert, M., Montani, D., Girerd, B., Scelsi, L., Ghio, S., Gall, H., Ghofrani, A., Bogaard, H. J., Noordegraaf, A. V., Houweling, A. C., Veld, A. H. i.’t., and Schotte, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Nature Communications 12: 7104
• Publisher Policy: Reproduced under a Creative Commons License