Innovation through collaboration at the intersection of childhood development and cancer: a platform for the Gabriella Miller Kids First Pediatric DataResource Center

通过在儿童发育和癌症交叉领域的合作进行创新：Gabriella Miller Kids First 儿科数据资源中心的平台

• 批准号: 10017435
• 负责人: Brandi Nicole Davis-Dusenbery
• 金额: $ 104.57万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-25 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017435
• 关键词: Acute Lymphocytic Leukemia; Address; Adult; Age; Automobile Driving; Basic Science; Big Data; Bioinformatics; Catalogs; Charge; Child; Childhood; Childhood Leukemia; Clinical; Clinical Data; Collaborations; Common Data Element; Communities; Complex; Complex Analysis; Congenital Abnormality; Congenital Heart Defects; Data; Data Scientist; Data Set; Data Sources; Development; Diagnosis; Disease; Down Syndrome; Ecosystem; Emerging Technologies; Ensure; Foundations; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genomic Data Commons; Genomics; Genotype; Growth; Health system; Healthcare; Heterogeneity; Individual; Infrastructure; Intellectual functioning disability; International; Investigation; Location; Longevity; Malignant Childhood Neoplasm; Malignant Neoplasms; Molecular; Neurodevelopmental Disorder; Online Systems; Patients; Pediatric Research; Pediatric cohort; Phenotype; Process; Rare Diseases; Research; Research Personnel; Research Project Grants; Risk; Role; Sampling; Speed; Standardization; Structural Congenital Anomalies; Technology; The Cancer Genome Atlas; Translational Research; Treatment outcome; United States National Institutes of Health; Ursidae Family; Work; base; big biomedical data; cancer genomics; clinical application; cohort; data access; data hub; data integration; data resource; data sharing; data warehouse; empowered; genome sequencing; genomic data; genomics cloud; high reward; high risk; improved; innovation; instrument; interoperability; multidisciplinary; neurobehavior; novel; novel therapeutics; parity; pediatric patients; personalized medicine; petabyte; phenotypic data; precision medicine; prevent; programs; rare cancer; tool; web portal; whole genome

Down syndrome (DS), the most common genetic form of intellectual disability, is associated with significant functional heterogeneity. One of the largest barriers to understanding the basis for this heterogeneity is that existing data are heterogeneous and disaggregated; this severely limits both computational utility and clinical applicability. Through partnership with the INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project and the Gabriella Miller Kids First Pediatric Research Program (Kids First), whole genome sequencing is being performed on over 6,000 samples for individuals with DS. The data from these samples will be used by a number of research projects towards understanding the genetic etiology underlying increased risk of congenital heart defects (CHD) and acute lymphoblastic leukemia (ALL) in children with Down Syndrome (DS). The Kids First Data Resource Center (DRC) will ensure genomic harmonization of these samples with other pediatric data generated by Kids First and other associated genomic datasets. The DRC also performs clinical data harmonization on a core set of fields across a wide variety of pediatric disease types, as there is recognition that increased standardization and computability increase the speed of scientific discovery. With the INCLUDE cohort, there is an opportunity to expand these capabilities towards improved harmonization of clinical instruments, especially in the domain of neurobehavior. Through this supplement, the assembled team will combine their expertise to overcome existing hurdles via two tasks: 1) Perform DS data standardization and 2) Extend DRC tooling and interfaces to support the Down Syndrome INCLUDE project. Together these two tasks will enable INCLUDE to expand DS cohorts and provide rapid ways to build new DS cohorts with common data elements, and to conduct high-risk/high reward genotype/phenotype studies to discover dysregulated genes on the trisomy 21 background followed by basic science studies. Moreover, this work could be expanded to other Kids First and trans-NIH initiatives in neurodevelopmental disorders.

唐氏综合症（DS）是智力障碍最常见的遗传形式，与显着的功能异质性相关。理解这种异质性基础的最大障碍之一是现有数据是异质且分散的；这严重限制了计算实用性和临床适用性。通过与“了解唐氏综合症的生命周期共存状况调查”(INCLUDE) 项目和 Gabriella Miller Kids First 儿科研究计划 (Kids First) 合作，目前正在对 6,000 多个唐氏综合症患者样本进行全基因组测序。这些样本的数据将被许多研究项目用来了解唐氏综合症 (DS) 儿童先天性心脏缺陷 (CHD) 和急性淋巴细胞白血病 (ALL) 风险增加的遗传病因。 Kids First 数据资源中心 (DRC) 将确保这些样本与 Kids First 生成的其他儿科数据和其他相关基因组数据集的基因组协调一致。 DRC 还对多种儿科疾病类型的核心领域进行临床数据协调，因为人们认识到标准化和可计算性的提高可以提高科学发现的速度。通过 INCLUDE 队列，我们​​有机会扩展这些能力，以改善临床仪器的协调性，特别是在神经行为领域。通过此补充，组建的团队将结合他们的专业知识，通过两项任务克服现有障碍：1) 执行 DS 数据标准化；2) 扩展 DRC 工具和接口以支持唐氏综合症 INCLUDE 项目。这两项任务将使 INCLUDE 能够扩展 DS 队列，并提供快速方法来构建具有通用数据元素的新 DS 队列，并进行高风险/高回报基因型/表型研究，以发现 21 三体性背景上失调的基因，然后进行基础研究科学研究。此外，这项工作可以扩展到其他“儿童优先”和跨 NIH 神经发育障碍项目。