Systems Biology of Early Atopy (SUNBEAM) Analysis and Bioinformatics Center

项目摘要 食物过敏（FA）和特应性皮炎（AD）是常见的慢性特应性疾病，分别占10%和20%。 孩子们，分别。FA患者每天都有可能发生危及生命的荨麻疹、血管性水肿， 呼吸困难、心血管损害、胃肠道不适和/或过敏反应， 食物中的抗原会使它们过敏。患有AD的个体必须与慢性胃炎， 发炎的皮肤可以覆盖他们身体的很大一部分并被感染。的发展 FA通常先于AD，提示共有的风险因素和重叠的病理生物学。FA和AD是 复杂的疾病，解析隐藏在其临床保护伞下的生物异质性至关重要 改善其预防、诊断和临床管理。一种系统生物学方法， 在多个层次上对FA和AD的生物学进行全面研究可能有助于确定新的知识 关于过敏的发展。系统生物学早期特应性（SunBEAm）是一个一般人群出生前 由NIAID发起的队列研究，旨在研究遗传、临床、生物学和 环境早期生活因素在过敏性疾病的发展，重点是FA和AD。 孕妇、她们所生的孩子和孩子的生父都被登记， 通过纵向生物样品收集进行表型分析。SunBEAm的一个中心目标是将系统生物学应用于 确定FA、AD及其内源性的发生机制和生物标志物。的 这个SunBEAm分析和生物信息学中心（ABC）应用程序的首要目标是创建一个 使用组学分析SunBEAm生物样品的中心，并将综合系统生物学应用于 确定FA和AD新决定因素。我们的应用集中在这五个具体目标：（1）分析 来自SunBEAm参与者的生物样本生成纵向、多尺度的组学数据，为研究提供信息 FA和AD的开发;（2）分析产生的系统范围的组学数据以鉴定新的生物标志物， 内型，以及FA和AD发生的潜在机制;（3）整合分子生物学数据， 确定FA和AD发展的关键驱动因素和预测因素的维度;（4）共享所有生成的数据， 为SunBEAm数据和生物信息学创新创建一个集中平台，并为 未来SunBEAm组学数据的集成;（5）开发与SunBEAm交互的基础设施 指导小组、NIAID统计和临床协调中心和NIAID。有了这个奖项，我们将 创建一个前所未有的系统过敏研究中心。除了一个调查小组与世界- 在多组学，系统生物学，计算生物学，数据科学和生物信息学方面的专业知识，我们的 该团队还包括直接设计并继续积极推动 SunBEAm的持续招募和实施。我们团队的经验、专业知识和经过验证的跟踪 记录将确保SunBEAm-ABC的成功。

PROJECT SUMMARY Food allergy (FA) and atopic dermatitis (AD) are common chronic conditions of atopy affecting 10% and 20% of children, respectively. Individuals with FA are at daily risk for potentially life-threatening hives, angioedema, respiratory difficulty, cardiovascular compromise, gastrointestinal distress, and/or anaphylaxis following ingestion of a food antigen to which they are sensitized. Individuals with AD must live with chronically pruritic, inflamed skin that can cover a significant proportion of their bodies and become infected. The development of FA is frequently preceded by AD, suggesting shared risk factors and overlapping pathobiology. FA and AD are complex diseases, and parsing the biological heterogeneity hidden under their clinical umbrellas is paramount to improving their prevention, diagnosis, and clinical management. A systems biology approach where the biology of FA and AD are investigated comprehensively at several levels may help identify new knowledge about the development of allergy. Systems Biology of Early Atopy (SunBEAm) is a general population pre-birth cohort study initiated by the NIAID to study the role and inter-relationships of genetic, clinical, biological, and environmental early-life factors in the development of allergic diseases, with an emphasis on FA and AD. Pregnant women, children born to them, and the children's biological fathers are being enrolled and phenotyped with longitudinal biosample collections. A central goal of SunBEAm is to apply systems biology to identify mechanisms and biomarkers underlying the development of FA, AD, and their endotypes. The overarching goal of this SunBEAm Analysis & Bioinformatics Center (ABC) application is to create a center for assaying SunBEAm biosamples using omics, and to apply integrative systems biology to identify novel determinants of FA and AD. Our application centers on these five specific aims: (1) Assay biosamples from SunBEAm participants to generate longitudinal, multi-scale omic data that will inform on the development of FA and AD; (2) Analyze the systems-wide omic data generated to identify novel biomarkers, endotypes, and mechanisms underlying the development of FA and AD; (3) Integrate data across molecular dimensions to identify key drivers and predictors of FA and AD development; (4) Share all generated data, create a centralized platform for SunBEAm data and bioinformatic innovations, and build capacity for the integration of future SunBEAm omics data; and (5) Develop infrastructure for interactions with the SunBEAm Steering Group, the NIAID Statistical and Clinical Coordinating Center, and NIAID. With this award, we will create a center for unprecedented systems allergy research. In addition to an investigator team with world- class expertise in multi-omics, systems biology, computational biology, data science, and bioinformatics, our team also includes physician-scientists and immunologists who directly designed and continue to actively drive the ongoing enrollment and implementation of SunBEAm. Our team's experience, expertise, and proven track record will ensure the success of SunBEAm-ABC.