Department of Medicine, National Heart and Lung Institute, Imperial College London, United Kingdom (C.J.R.).
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.A.M.).
Circ Res. 2022 Apr 29;130(9):1423-1444. doi: 10.1161/CIRCRESAHA.121.319969. Epub 2022 Apr 28.
Pulmonary hypertension is a complex disease with multiple causes, corresponding to phenotypic heterogeneity and variable therapeutic responses. Advancing understanding of pulmonary hypertension pathogenesis is likely to hinge on integrated methods that leverage data from health records, imaging, novel molecular -omics profiling, and other modalities. In this review, we summarize key data sets generated thus far in the field and describe analytical methods that hold promise for deciphering the molecular mechanisms that underpin pulmonary vascular remodeling, including machine learning, network medicine, and functional genetics. We also detail how genetic and subphenotyping approaches enable earlier diagnosis, refined prognostication, and optimized treatment prediction. We propose strategies that identify functionally important molecular pathways, bolstered by findings across multi-omics platforms, which are well-positioned to individualize drug therapy selection and advance precision medicine in this highly morbid disease.
肺动脉高压是一种病因复杂的疾病,对应表型异质性和可变的治疗反应。深入了解肺动脉高压的发病机制可能取决于整合利用健康记录、影像学、新型分子组学分析和其他模式的数据的综合方法。在这篇综述中,我们总结了该领域迄今为止产生的关键数据集,并描述了具有解析潜在支持肺血管重构分子机制的分析方法,包括机器学习、网络医学和功能遗传学。我们还详细介绍了遗传和亚表型方法如何实现更早的诊断、更精确的预后预测和优化的治疗预测。我们提出了一些策略,通过跨多组学平台的发现来确定功能重要的分子途径,这些策略很有希望实现药物治疗选择的个体化,并在这种高度病态的疾病中推进精准医学。