Data Management and Portal for the INCLUDE (DAPI) Project

INCLUDE (DAPI) 项目的数据管理和门户

• 批准号: 10264912
• 负责人: Robert J Carroll
• 金额: $ 386.95万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-26 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264912
• 关键词: Advocacy; Advocate; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid Beta A4 Precursor Protein; Area; Autoimmune Diseases; Automobile Driving; Biomedical Research; Chromosome 21; Chromosomes; Clinic; Clinical; Cohort Studies; Collaborations; Communities; Complex; Data; Data Coordinating Center; Data Set; Development; Discipline; Disease; Down Syndrome; Ecosystem; Ensure; Environmental Risk Factor; Epigenetic Process; Epilepsy; Family; General Population; Genetic Diseases; Genetic Variation; Goals; Government; Government Officials; Human; Human Biology; Individual; Intuition; Investigation; Life Cycle Stages; Life Expectancy; Link; Longevity; Malignant Neoplasms; Methods; Mission; Modality; Neurologic; Participant; Pathogenicity; Phenotype; Physicians; Population; Proteome; Quality of life; Research; Resources; Risk; Scientist; Societies; Solid; Surveys; Technology; Time; TimeLine; Training and Education; United States National Institutes of Health; Variant; autism spectrum disorder; base; bench to bedside; biobank; comorbidity; congenital heart disorder; data access; data ecosystem; data management; data portal; data resource; data sharing; data sharing networks; design; diverse data; empowered; epidemiology study; evidence base; innovation; interoperability; leukemia; lifestyle factors; metabolome; microbiome; multiple omics; novel; novel diagnostics; novel therapeutics; outreach; precision medicine; prenatal; synergism; tool; transcriptome; virtual

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.

项目摘要 - 总体。 患有唐氏综合症（DS）的个体是由21（T21）引起的遗传条件，倾向于 异质性疾病的频谱，同时保护了其他病原 相对于典型人群的条件。 T21以仍然不太定义的方式保护个人免受最稳固的侵害 恶性肿瘤虽然强烈诱使他们患阿尔茨海默氏病，先天性心脏病，白血病， 自身免疫性疾病和潜水神经系统疾病。但是，对机制知之甚少 在DS与DS的背景下，这种差异临床概况或这些条件之间的关系 发生在普通人群中时。此外，患有DS的人显示大量表型 变异表明存在调节因素的存在，这些因素影响了T21在个体级别表现的方式， 包括遗传变异，表观遗传修饰剂，不同的内型调节转录组，蛋白质组和 代谢组，生活方式和环境因素，甚至是微生物组。因此，阐明 驾驶和调节DS合并症的机制不仅可以为全球600万人提供服务 DS今天还活着，但也有数百万人在典型人群中受这些合并症的影响。这 NIH通过推出了这一事实的重要性（调查 整个寿命的同时存在条件，以了解唐氏综合症）项目。 在此框架内，包括项目已经认识到大型队列研究的战略重要性 具有DS的人可以加速该领域的研究，目的是实现精确医学方法 通过新颖的诊断和治疗工具到DS。因此，该DCC团队的任务是创建一个世界 - 集体资源和相关平台，用于授权数据共享，数据访问和集成分析， 将对整个生命周期的所有DS合并症进行新的调查。为了实现这一目标，提议 DCC将创建一个实时，集成的数据生态系统，将催化创新，协作和 通过参与和授权利益相关者的潜水员社区驾驶的能力来推动变革性发现 合作，加速的发现，代表基准的变革行动和影响 超过。总的来说，拟议努力的基础的努力将为DS的第一和外国人民服务 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 潜水员科学学科。