Pediatric Autoimmune Consortium for Exposome Research (PACER)

项目摘要 虽然自身免疫性疾病(AID)在整个生命周期内都会发生，但许多AID的最早迹象可以首先在 儿童和青少年。早期发病可能与更具侵袭性的病程和 并发症会随着时间的推移而积累。尽管疾病实体之间在受影响的组织和 对于危险因素的发生，值得注意的是重要的共同主题在致病因素中，从重叠在 潜在环境诱因的风险基因。自身免疫性疾病发病率的总体上升表明 影响风险的持续环境变化。了解可改变的暴露对疾病的影响 发病机制有可能提供有针对性的干预措施，从而减缓或阻止疾病的发展和 这些疾病在儿童和成年后的发展。 我们建议建立一个新的、首屈一指的跨学科研究团队来开发 基础设施治疗需要用于未来关于曝光体在儿童艾滋病中的作用的大规模研究。我们的 总体目标是：1)建立协作伙伴关系，以利用现有群体和资源；2) 开发一种多领域、多层次的方法来全面研究曝光体在艾滋病中的作用 途径；以及3)开发新的策略，利用切割来整合环境因素和遗传数据 先进的数据科学方法，以调查儿童艾滋病的发展和进展。我们的特定 目标是： 目标1：建立多学科研究团队，发展合作伙伴关系，研究 儿童艾滋病暴露组，通过(1A)建立一个跨学科联盟，跨越现有的研究 儿童艾滋病)；(1B)对相关的现有资源进行景观分析；(1C)组织两个 为期数天的研讨会，以发展和扩大现有的研究和合作。 目标2：探讨应对全面衡量所需的多领域、多层次办法的战略 暴露和评估结构以评估其对艾滋病儿童疾病途径的影响(2A) 全面分析测量和分析早期生命曝光物的现有方法 (2b)开发和推广综合多种数据类型的数据科学方法，以确定准确的风险概况， 以及(2C)通过对现有数据进行试点分析，展示这些方法的实用性。 目标3：开发和实施研究基础设施，以支持未来的确切工作。 影响：拟议的研究活动将为未来大规模的国家、 跨学科的协作研究网络，专注于在儿童时期进行开创性的研究 援助。

Project Summary While autoimmune disease (AID) occurs across the lifespan, the earliest signs of many AID can first be seen in children and adolescents. Early onset of disease can be associated with more aggressive course and the risk of complications accumulate over time. Despite diversity amongst disease entities in terms of tissues affected and risk factors for occurrence, it is striking to note important common themes in pathogenic factors, from overlap in risk genes to potential environmental triggers. The overall rising incidence of autoimmune diseases suggests ongoing enviromenal changes which impact risk. Understanding the impact of modifiable exposures on disease pathogenesis has the potential to inform targeted interventions that could slow or prevent the development and progression of these diseases in children and later adulthood. We propose to develop a new, first-of-its-kind transdisplinary research team to developing the infrasturcure needed to for a future large scale study on the role of the exposome in childhood AID. Our overarching goals are to: 1) establish collaborative partnerships to leverage existing cohorts and resources; 2) develop a multidomain, multilevel approach to comprehensively examine the role of the exposome on AID pathways; and 3) develop novel strategies for integrating environmental factors and genetic data using cutting- edge data science methodologies to investigate the development and progression of childhood AID. Our specific aims are: Aim 1: To establish a multidisciplinary research team and develop collaborative partnerships for studying the exposome in childhood AID by (1A) developing a transdisciplinary consortium across existing studies of childhood AID); (1B) conducting a landscape analysis of relevant existing resources; and (1C) organizing two multiday workshops to develop and expand existing research and collaborations. Aim 2: Explore strategies to address the multidomain, multilevel approach needed to comprehensively measure the exposome and assess constructs to evaluate their effect on disease pathways in children with AID by (2A) conducting a comprehensive analysis of existing methods for measuring and analyzing the early-life exposome (2B) develop and expand data science methods for integrating multiple data types to identify precise risk profiles, and (2C) demonstrate the utility of these approaches by generating pilot analysis in existing data. Aim 3: Develop and implement research infrastructure to support the future EXACT effort. IMPACT: The proposed research activities will lay the foundations for future large scale national, interdisciplinary, collaborative research network focused on performing groundbreaking research in childhood AID.