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dc.contributor.authorKariotis, Sokratis
dc.contributor.authorJammeh, Emmanuel
dc.contributor.authorSwietlik, Emilia M
dc.contributor.authorPickworth, Josephine A
dc.contributor.authorRhodes, Christopher J
dc.contributor.authorOtero, Pablo
dc.contributor.authorWharton, John
dc.contributor.authorIremonger, James
dc.contributor.authorDunning, Mark J
dc.contributor.authorPandya, Divya
dc.contributor.authorMascarenhas, Thomas S
dc.contributor.authorErrington, Niamh
dc.contributor.authorThompson, AA Roger
dc.contributor.authorRomanoski, Casey E
dc.contributor.authorRischard, Franz
dc.contributor.authorGarcia, Joe GN
dc.contributor.authorYuan, Jason X-J
dc.contributor.authorAn, Tae-Hwi Schwantes
dc.contributor.authorDesai, Ankit A
dc.contributor.authorCoghlan, Gerry
dc.contributor.authorLordan, Jim
dc.contributor.authorCorris, Paul A
dc.contributor.authorHoward, Luke S
dc.contributor.authorCondliffe, Robin
dc.contributor.authorKiely, David G
dc.contributor.authorChurch, Colin
dc.contributor.authorPepke-Zaba, Joanna
dc.contributor.authorToshner, Mark
dc.contributor.authorWort, Stephen
dc.contributor.authorGraf, Stefan
dc.contributor.authorMorrell, Nicholas W
dc.contributor.authorWilkins, Martin R
dc.contributor.authorLawrie, Allan
dc.contributor.authorWang, Dennis
dc.contributor.authorUK National PAH Cohort Study Consortium
dc.date.accessioned2021-12-24T14:37:11Z
dc.date.available2021-12-24T14:37:11Z
dc.date.issued2021-12-07
dc.date.submitted2020-10-27
dc.identifier.issn2041-1723
dc.identifier.others41467-021-27326-0
dc.identifier.other27326
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331801
dc.description.abstractIdiopathic 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/114/1386
dc.subject/631/114/2404
dc.subject/631/1647/2217
dc.subject/692/4019/592/75
dc.subject/38/91
dc.subject/49/39
dc.subjectarticle
dc.titleBiological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.
dc.typeArticle
dc.date.updated2021-12-24T14:37:10Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.79250
dcterms.dateAccepted2021-11-15
rioxxterms.versionofrecord10.1038/s41467-021-27326-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidKariotis, Sokratis [0000-0001-9993-6017]
dc.contributor.orcidPickworth, Josephine A [0000-0002-7199-364X]
dc.contributor.orcidRhodes, Christopher J [0000-0002-4962-3204]
dc.contributor.orcidWharton, John [0000-0001-8110-2575]
dc.contributor.orcidIremonger, James [0000-0003-3953-8812]
dc.contributor.orcidDunning, Mark J [0000-0002-8853-9435]
dc.contributor.orcidErrington, Niamh [0000-0001-6768-7394]
dc.contributor.orcidThompson, AA Roger [0000-0002-0717-4551]
dc.contributor.orcidHoward, Luke S [0000-0003-2822-210X]
dc.contributor.orcidGraf, Stefan [0000-0002-1315-8873]
dc.contributor.orcidWilkins, Martin R [0000-0003-3926-1171]
dc.contributor.orcidLawrie, Allan [0000-0003-4192-9505]
dc.contributor.orcidWang, Dennis [0000-0003-0068-1005]
dc.identifier.eissn2041-1723
pubs.funder-project-idMedical Research Council (MR/K020919/1)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (SP/18/10/33975)
cam.issuedOnline2021-12-07


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