Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.
Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.
复制标题
DOI：
10.1038/s41467-021-27326-0
复制
发表时间：
2021-12-07
影响因子：
16.6
通讯作者：
UK National PAH Cohort Study Consortium
中科院分区：
文献类型：
--
作者：
Kariotis S;Jammeh E;Swietlik EM;Pickworth JA;Rhodes CJ;Otero P;Wharton J;Iremonger J;Dunning MJ;Pandya D;Mascarenhas TS;Errington N;Thompson AAR;Romanoski CE;Rischard F;Garcia JGN;Yuan JX;An TS;Desai AA;Coghlan G;Lordan J;Corris PA;Howard LS;Condliffe R;Kiely DG;Church C;Pepke-Zaba J;Toshner M;Wort S;Gräf S;Morrell NW;Wilkins MR;Lawrie A;Wang D;UK National PAH Cohort Study Consortium
特发性肺动脉高压（IPAH）是一种罕见但致命的疾病，通过右心导管插入术诊断，排除其他形式的肺动脉高压，产生了具有不同治疗反应的异质性人群。在这里，我们展示了三个主要患者亚组的无监督机器学习识别，这些亚组占队列的92%，每个亚组都具有独特的全血转录组和临床特征。这些亚组与不良、中度和良好预后相关。预后不良的亚组与ALAS 2的上调和几种免疫球蛋白基因的下调相关，而预后良好的亚组由骨形态发生蛋白信号转导调节剂NOG和HLA-DPA 1/DPB 1的C/C变体（与生存独立相关）的上调定义。这些独立验证的发现为IPAH分类中存在3个主要亚组（内表型）提供了证据，可以改善风险分层，并为IPAH的发病机制提供分子见解。特发性肺动脉高压是一种罕见的致死性疾病，治疗反应不均匀。在这里，作者表明，对359名特发性肺动脉高压患者的全血转录组进行无监督机器学习，识别出3个亚组（内表型），可以改善风险分层并提供新的分子见解。
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. Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.
登录
查看更多内容
影响因子：
2.6
作者：
Bergemann R;Allsopp J;Jenner H;Daniels FA;Drage E;Samyshkin Y;Schmitt C;Wood S;Kiely DG;Lawrie A;SPHInX Project team
通讯作者：
SPHInX Project team
影响因子：
16.6
作者：
Gräf S;Haimel M;Bleda M;Hadinnapola C;Southgate L;Li W;Hodgson J;Liu B;Salmon RM;Southwood M;Machado RD;Martin JM;Treacy CM;Yates K;Daugherty LC;Shamardina O;Whitehorn D;Holden S;Aldred M;Bogaard HJ;Church C;Coghlan G;Condliffe R;Corris PA;Danesino C;Eyries M;Gall H;Ghio S;Ghofrani HA;Gibbs JSR;Girerd B;Houweling AC;Howard L;Humbert M;Kiely DG;Kovacs G;MacKenzie Ross RV;Moledina S;Montani D;Newnham M;Olschewski A;Olschewski H;Peacock AJ;Pepke-Zaba J;Prokopenko I;Rhodes CJ;Scelsi L;Seeger W;Soubrier F;Stein DF;Suntharalingam J;Swietlik EM;Toshner MR;van Heel DA;Vonk Noordegraaf A;Waisfisz Q;Wharton J;Wort SJ;Ouwehand WH;Soranzo N;Lawrie A;Upton PD;Wilkins MR;Trembath RC;Morrell NW
通讯作者：
Morrell NW
影响因子：
82.9
作者：
Fresard, Laure;Smail, Craig;Dyment, David
通讯作者：
Dyment, David
影响因子：
9.6
作者：
Benza, Raymond L.;Gomberg-Maitland, Mardi;Frantz, Robert P.
通讯作者：
Frantz, Robert P.
影响因子：
24.3
作者：
Hoeper, Marius M.;Kramer, Tilmann;Gruenig, Ekkehard
通讯作者：
Gruenig, Ekkehard