Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Victoria, Australia.
School of BioSciences, The University of Melbourne, Victoria, Australia.
Elife. 2018 Oct 15;7:e35856. doi: 10.7554/eLife.35856.
Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.
生命早期的事件会导致随后患哮喘的风险增加；然而，儿童喘息的病因和轨迹是异质的，并不总是导致哮喘。同样，并非所有特应性个体都会出现喘息，反之亦然。这些差异的原因尚不清楚。我们使用无监督基于模型的聚类分析，在具有深入免疫和呼吸表型的前瞻性出生队列中确定了潜在的聚类。我们根据免疫特征和疾病风险对每个聚类进行了描述，并在来自英国和美国的外部队列中复制了我们的结果。我们发现了三种不同的轨迹，其中一种是高风险的“特应性”聚类，在整个儿童期更容易患过敏性疾病。特应性因聚类成员而异，对以后的喘息有不同的影响。我们的研究结果表明，无监督分析在阐明哮喘发病机制的异质性方面具有实用性，并为改善儿童哮喘的管理和预防提供了基础。
