Data Management and Portal for the INCLUDE (DAPI) Project

项目概要-总体。 唐氏综合征（DS）是由21三体（T21）引起的遗传疾病， 一系列异质性疾病，同时防止发展为其他致病性疾病 相对于普通人群而言。T21在某些方面仍然定义不清，它可以保护个人免受大多数固体物质的侵害。 恶性肿瘤，而强烈倾向于他们阿尔茨海默氏病，先天性心脏病，白血病， 自身免疫性疾病和各种神经系统疾病然而，人们对这些机制知之甚少， 作为这种差异性临床特征的基础，或在DS背景下这些疾病与 在一般人群中发生。此外，患有DS的个体显示出很大程度的表型 变异表明存在影响T21如何在个体水平上表现的调节因素， 包括遗传变异、表观遗传修饰物、调节转录组、蛋白质组和 代谢组、生活方式和环境因素，甚至可能是微生物组。因此，阐明 驱动和调节DS合并症的机制不仅将为全球600万人提供服务， DS今天还活着，但在典型人群中也有数百万人受到这些合并症的影响。的 NIH通过启动INCLUDE（INVESTIGATION OF 了解唐氏综合征项目的寿命范围内的共现情况。 在这一框架内，INCLUDE项目认识到了开展一项大型队列研究的战略重要性， 患有DS的个人加速这一领域的研究，目标是实现精准医学方法 通过新的诊断和治疗工具转化为DS。因此，这个DCC团队的使命就是创造一个世界- 类资源和相关平台，用于授权数据共享、数据访问和集成分析， 将能够对整个生命周期内的所有DS合并症进行新的研究。为实现这一目标，建议 DCC将创建一个实时、集成的数据生态系统，促进创新、协作和 变革性的发现，通过参与和授权不同的利益相关者社区， 协作，加速发现，代表从实验室到床边的变革行动和影响， 超越。总而言之，支持拟议工作的努力将首先服务于DS患者 通过加速对DS合并症的研究，但也将提高我们对人类生物学的理解， 不同的科学学科。

PROJECT SUMMARY – Overall. Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), are predisposed to a spectrum of heterogeneous diseases while simultaneously protected from developing other pathogenic conditions relative to the typical population. In ways still poorly defined, T21 protects individuals from most solid malignancies while strongly predisposing them to Alzheimer’s disease, congenital heart disease, leukemias, autoimmune disorders, and diverse neurological conditions. However, little is known about the mechanisms underlying this differential clinical profile or the relationship between these conditions in the context of DS versus when occurring in the general population. Moreover, individuals with DS display a large degree of phenotypic variation suggesting the existence of modulating factors that affect how T21 manifests at the individual level, including genetic variation, epigenetic modifiers, varying endotypes modulating the transcriptome, proteome and metabolome, lifestyle and environmental factors, or even perhaps the microbiome. Therefore, elucidating the mechanisms driving and modulating DS comorbidities will serve not only the six million people worldwide with DS alive today, but also millions of individuals affected by these comorbidities in the typical population. The importance of this fact has been acknowledged by NIH through the launching of the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project. Within this framework, the INCLUDE Project has recognized the strategic importance of a large cohort study of individuals with DS to accelerate research in this area, with the goal of enabling a precision medicine approach to DS via novel diagnostics and therapeutic tools. Therefore, the mission of this DCC team is to create a world- class resource and associated platforms for empowered data sharing, data access, and integrative analysis that will enable novel investigations into all DS comorbidities across the lifespan. To achieve this goal, the proposed DCC will create a real-time, integrated data ecosystem that will catalyze innovation, collaboration, and transformative discoveries by engaging and empowering a diverse community of stakeholders to drive collaborative, accelerated discovery on behalf of transformative action and impact from bench to bedside and beyond. Altogether, the efforts underpinning the proposed efforts will serve first and foremost people with DS by accelerating research into DS comorbidities, but will also elevate our understanding of human biology across diverse scientific disciplines.