Data Management and Portal for the INCLUDE (DAPI) Project

项目总结--总体。 唐氏综合征(DS)是由21三体(T21)引起的遗传疾病，其个体容易患上 异质疾病谱，同时保护免受其他病原体的影响 相对于典型人群的条件。T21以一种仍然定义不清的方式保护个人免受最坚固的 恶性肿瘤虽然极易导致阿尔茨海默氏症、先天性心脏病、白血病， 自身免疫性疾病和不同的神经疾病。然而，人们对这种机制知之甚少。 在DS和VS的背景下，这种不同的临床特征或这些情况之间的关系 当发生在普通人群中时。此外，患有DS的个体表现出很大程度的表型 变异表明存在影响T21在个体水平表现的调节因素， 包括遗传变异、表观遗传修饰物、调节转录组的不同内型、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，澄清 驱动和调节DS合并症的机制将不仅服务于全球600万人 DS活到今天，但也有数百万人受到这些共生疾病的影响，在典型人群中。这个 这一事实的重要性已被NIH通过发起Include(调查 在了解唐氏综合症的整个生命周期中发生的情况)项目。 在这一框架内，Include项目认识到对以下项目进行大规模队列研究的战略重要性 DS患者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达到DS。因此，这个DCC团队的使命是创造一个世界-- 支持数据共享、数据访问和集成分析的类资源及相关平台 将使对所有DS共病的新研究成为可能。为达到这一目标，建议的 DCC将创建实时、集成的数据生态系统，以促进创新、协作和 通过让不同的利益相关者社区参与并为其提供动力来推动变革发现 协作、加速发现，代表从工作台到床边的转型行动和影响 更远一点。总之，支持拟议努力的努力将首先服务于DS患者 通过加速对DS共病的研究，还将提高我们对整个人类生物学的理解 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.