Advancing the cloud-based data access and interoperability infrastructure of the INCLUDE data ecosystem

推进 INCLUDE 数据生态系统基于云的数据访问和互操作性基础设施

• 批准号: 10596806
• 负责人: Jack DiGiovanna
• 金额: $ 33.09万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596806
• 关键词: Affect; Alzheimer' s Disease; Amyloid Beta A4 Precursor Protein; Authorization documentation; Autoimmune Diseases; Automobile Driving; Chromosome 21; Chromosomes; Clinical; Communities; Computer software; Custom; Data; Disease; Down Syndrome; Environmental Risk Factor; Epigenetic Process; Epilepsy; Feedback; Genetic Variation; Goals; Individual; Infrastructure; Life Expectancy; Link; Malignant Neoplasms; National Heart, Lung, and Blood Institute; Neurologic; Persons; Phenotype; Population; Probability; Proteome; Quality of life; Research; Research Personnel; Risk; Secure; Services; Solid; System; United States National Institutes of Health; Variant; adjudicate; autism spectrum disorder; base; cloud based; comorbidity; congenital heart disorder; data access; data ecosystem; data hub; data interoperability; database of Genotypes and Phenotypes; design; epidemiology study; leukemia; lifestyle factors; metabolome; microbiome; transcriptome

PROJECT SUMMARY The overarching goal of the INCLUDE Data Hub is to serve all people with Down syndrome (DS) by accelerating the pace of discoveries into the mechanisms by which trisomy 21 (T21) predisposes these individuals to a wide range of comorbidities that shorten their life expectancy and diminish their quality of life. Over the last few decades, the life expectancy for people with DS has significantly increased, and epidemiological studies reveal that T21 causes a different disease spectrum, protecting these individuals from developing certain conditions, such as most solid malignancies (1,2), while strongly predisposing them to others, such as Alzheimer’s disease (AD) (3), congenital heart disease (CHD) (4), leukemias (1), autoimmune disorders (5–17), and neurological conditions such as autism and seizure disorders (18–22). With the exception of their increased risk of developing AD, which has been linked to the presence of the APP gene on chromosome 21 (3), little is known about the mechanisms underlying this differential clinical profile. Moreover, there is massive phenotypic variation among individuals with T21, which suggests the existence of factors modulating the effects of the extra chromosome, such as 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 INCLUDE Data Hub has reached a significant milestone of an MVP launch featuring both open-access and controlled data (via Kids First Gen3) on 21 March 2022. Here, we propose “Advancing the cloud-based data access and interoperability infrastructure of the INCLUDE data ecosystem” to empower more authorized researchers to access controlled INCLUDE data. This capability is beyond the scope of what we envision in the original INCLUDE DAPI proposal. Our focus is to develop and implement Clearinghouse software and integrate it with the DRS Server already developed for INCLUDE. The Clearinghouse receives and interprets the RAS Passport, and the custom visas contained, to ascertain the ability of a user to access controlled data (importantly, authorization continues to be governed by dbGaP). We will also provide feedback and advance the GA4GH specification pertinent to this effort, to drive these standards towards alignment with the INCLUDE Data Hub strategy.

项目摘要 INCLUDE数据中心的总体目标是通过加速为所有唐氏综合症（DS）患者提供服务， 21三体（T21）使这些个体倾向于广泛的遗传学机制的发现速度， 一系列缩短预期寿命并降低生活质量的合并症。过去几 几十年来，DS患者的预期寿命显着增加，流行病学研究表明， T21导致不同的疾病谱，保护这些个体免于发展某些疾病， 如大多数实体恶性肿瘤（1，2），同时强烈倾向于其他疾病，如阿尔茨海默氏病 (AD)（3）、先天性心脏病（CHD）（4）、白血病（1）、自身免疫性疾病（5-17）和神经系统疾病（5 - 17）。 条件，如自闭症和癫痫症（18-22）。除了他们的风险增加， AD的发生与21号染色体上APP基因的存在有关（3），但人们对此知之甚少 关于这种不同临床特征的机制。此外，有大量的表型 T21个体之间的差异，这表明存在调节额外的T21效应的因素。 染色体，如遗传变异，表观遗传修饰，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，我们认为， 阐明驱动和调节DS合并症的机制不仅可以为600万人服务， 在全球范围内，DS今天仍然存在，但在典型的 人口 INCLUDE数据中心已经达到了MVP发布的重要里程碑， 受控数据（通过Kids First Gen 3）于2022年3月21日发布。在这里，我们提出“推进基于云的数据 INCLUDE数据生态系统的访问和互操作性基础设施”， 研究人员访问受控的INCLUDE数据。这种能力超出了我们在 最初的INCLUDE DAPI提案。 我们的重点是开发和实施Clearinghouse软件，并将其与DRS服务器集成 为包容而发展。信息交换所接收并解释RAS护照和海关签证 包含，以确定用户访问受控数据的能力（重要的是，授权仍然是 由dbGaP管理）。我们还将提供反馈并推进与此相关的GA 4GH规范 努力推动这些标准与INCLUDE数据中心战略保持一致。