Statistical causal modelling approaches to understanding the developmental profiles of asthma and allergy

在过去的十年中，大数据挖掘取得了快速进展，纵向数据的聚类用于识别哮喘的各种发展概况以及分解过敏性致敏。该项目旨在通过超越当前的建模方法并专注于不同变量的数据整合来进一步推动这一领域的进展，从患者报告的结果到血液生物标志物和肺功能测量，该项目的主要数据来源将是五个基于人口的出生队列，这些队列构成了早期哮喘研究（STELAR）网络的一部分，在其他地方详细描述。总的来说，这些群组提供了超过14 000名儿童的数据，并具有类似的数据结构，这将有助于分析。在每个时间点，使用经验证的问卷收集有关喘息、特应性湿疹和鼻炎发生率和频率的信息。在某些时间点还记录了对不同变应原成分的IgE反应和各种肺功能指标。该项目的主要目标是发现临床相关的表型，这些表型是同质的，并且具有共同的潜在病理生理机制。虽然以前的研究使用数据驱动的方法来推导表型聚类，但迫切需要通过整合我们可用的更广泛的数据来完善这些聚类，并确保它们与结果相关并证明临床实用性。该项目的目标是在出生队列中复制研究结果，并可能通过不同的证据来验证它们，例如后期新生小鼠模型的数据。

The past decade has seen rapid advances in big data mining, with clustering of longitudinal data used to identify a variety of developmental profiles of asthma as well as to disaggregate allergic sensitisation. This project will aim to further the progress in this area by moving beyond current modelling approaches and focusing on data integration across different variables, from patient reported outcomes to blood biomarkers and lung function measurements.Main data sources for this project will be five population based birth cohorts that form part of the Study Team for Early Life Asthma Research (STELAR) network, which is described in detail elsewhere. Collectively, these cohorts provide data for > 14,000 children and have similar data structures that will facilitate analysis. At each time point, validated questionnaires were used for gathering information on the occurrence and frequency of wheezing, atopic eczema and rhinitis. IgE responses to different allergen components and various lung function measures were also recorded at some of the time points.A major goal of the project will be the discovery of clinically relevant phenotypes that are homogeneous and share underlying pathophysiological mechanisms. While previous studies have used data-driven approaches to derive phenotypic clusters, there is a pressing need to refine these by integrating a broader range of the data available to us, and make sure they relate to outcomes and demonstrate clinical utility. The project will aim to replicate findings across birth cohorts, and potentially verify them via disparate lines of evidence such as data from neonatal mouse models in later stages.