Data Management and Portal for the INCLUDE (DAPI) Project

INCLUDE (DAPI) 项目的数据管理和门户

• 批准号: 10697338
• 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/10697338
• 关键词: Acceleration; Advocacy; Advocate; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid Beta A4 Precursor Protein; Area; Autoimmune Diseases; Automobile Driving; Biomedical Research; Child; Chromosome 21; Chromosomes; Clinic; Clinical; Cohort Studies; Collaborations; Communities; Complex; Data; Data Coordinating Center; Data Set; Development; Discipline; Disease; Down Syndrome; Ecosystem; Education; 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; Multiomic Data; Neurologic; Participant; Pathogenicity; Persons; Phenotype; Physicians; Population; Proteome; Quality of life; Research; Resources; Risk; Schools; Scientist; Societies; Solid; Surveys; Technology; Time; Training; United States National Institutes of Health; Variant; autism spectrum disorder; bench to bedside; biobank; comorbidity; congenital heart disorder; data access; data ecosystem; data integration; data management; data portal; data resource; data sharing; data sharing networks; design; diverse data; empowerment; epidemiology study; evidence base; innovation; interoperability; leukemia; lifestyle factors; metabolome; microbiome; novel; novel diagnostics; novel therapeutics; outreach; precision medicine; prenatal; synergism; timeline; 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——总体而言。 唐氏综合症 (DS) 患者（由 21 三体 (T21) 引起的遗传病）容易患上 异质性疾病谱，同时防止其他致病性疾病的发展 相对于典型人群的条件，T21 可以保护个体免受大多数固体的侵害。 恶性肿瘤，同时极易患阿尔茨海默病、先天性心脏病、白血病、 然而，人们对其机制知之甚少。 这种差异性临床特征的基础或在 DS 与 DS 背景下这些条件之间的关系 此外，当发生在一般人群中时，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 在个体水平上表现的调节因素， 包括遗传变异、表观遗传修饰剂、调节转录组、蛋白质组和的不同内型 因此，阐明代谢组、生活方式和环境因素，甚至微生物组。 驱动和调节 DS 合并症的机制不仅将为全世界 600 万患有 DS 并发症的人提供服务 如今，DS 仍然存在，但在典型人群中还有数百万个体受到这些合并症的影响。 NIH 通过启动 INCLUDE（对 了解唐氏综合症的整个生命周期中同时发生的病症E) 项目。 在此框架内，INCLUDE 项目认识到大规模队列研究的战略重要性 DS 患者加速该领域的研究，目标是实现精准医疗方法 因此，DCC 团队的使命是创造一个世界—— 类资源和相关平台，用于授权数据共享、数据访问和综合分析 将使对整个生命周期中所有 DS 合并症进行新颖的研究成为可能。 DCC 将创建一个实时、集成的数据生态系统，以促进创新、协作和 通过吸引多元化的利益相关者社区并赋予其权力来推动变革性发现 协作、加速发现，代表从实验室到临床的变革行动和影响， 总而言之，支持拟议工作的努力将首先为 DS 患者服务。 通过加速对 DS 合并症的研究，也将提升我们对人类生物学的理解 多样化的科学学科。