Genome Sequencing in support of the Gabriella Miller Kids First Pediatric Research Program

基因组测序支持 Gabriella Miller Kids First 儿科研究计划

• 批准号: 10255505
• 负责人: Stacey Gabriel
• 金额: $ 277.47万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255505
• 关键词: All of Us Research Program; Back; Catalogs; Childhood; Clinical; Collaborations; Collection; Communities; Data; Databases; Defect; Detection; Diagnostic; Disease; Elements; Ensure; Evaluation; Family; Funding; Gene Frequency; Generations; Genes; Genetic; Genome; Genomics; Goals; Human Genome; Institutes; Intake; Intervention; Intuition; Large-Scale Sequencing; Libraries; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical Genetics; National Human Genome Research Institute; Output; Pathogenicity; Patients; Pediatric Research; Phase; Phenotype; Population Genetics; Preparation; Process; RNA Splicing; Research; Research Personnel; Resources; Role; Sampling; Structural Congenital Anomalies; Structure; The Cancer Genome Atlas; Therapeutic; Tissues; Trans-Omics for Precision Medicine; United States National Institutes of Health; Variant; Work; base; causal variant; cohort; computerized data processing; cost; data analysis pipeline; data exploration; data harmonization; data integration; data management; data resource; data sharing; data standards; exome; flexibility; gene discovery; genome analysis; genome sequencing; genomic data; interest; large datasets; programs; success; targeted treatment; tool; transcriptome sequencing; whole genome

We propose to continue to provide data generation and processing activities that will enrich a genomic data resource to propel pediatric disease research. Key elements to a successful program will be the provision of high quality genome sequence data on well-phenotyped patients and their families; the collection and accessibility of data to the research community in an intuitive manner; and the integration of genetic data with phenotypic information in the context of this program and comparison to other large data resources. The ultimate goal is to assemble a complete catalogue of genes that underlie structural birth defects and pediatric cancer and to enable the use of this information to better understand disease mechanism, diagnostic opportunities and therapeutic direction. We propose to continue as a Kids First Sequencing Center at the Broad Institute as we have done for the past three years for the program and as we have also done in support of other large flagship NIH genome projects. Our center brings the domain expertise is high throughput data generation, processing and analysis, and disease gene discovery required to meet the objectives of the Kids First Program. We will apply deep, high-quality whole genome sequencing data on selected samples. We will be flexible to work closely and accommodate the needs and interests of selected X01 Investigators. Over the next three- year period we can provide for as many as 25,000 samples pushing the boundary on new data types and lower cost. We are flexible to a mix of cohort types, whether they are trio based (for structural birth defects) or quads (in cancer studies). We will work with X01 Investigators to introduce new data types such as RNASeq or Long Read Sequencing when appropriate. We will participate in the evaluation of these data types and their overall impact on discovery and scientific output of the program A key feature of our center is our implementation of a robust analytical framework for variant assessment and disease gene discovery, which builds on Broad investigators’ world-leading roles in statistical genetics, functional annotation, and clinical variant interpretation as well as access to exome and genome data from hundreds of thousands of samples sequenced at Broad. This has enabled us to build a systematic pipeline for gene discovery that will be made freely available to the Kids First program. With data produced and processed in a consistent way, we can offer seamless integration of Kids First data into our analytic framework. For many of the diseases targeted by pediatric research community, confident discovery of causal genes will require aggregation of cases across centers around the world. We will partner with the Kids First Data Resource Center in a variety of ways to ensure that the program is well-aligned with other large-scale resource generation projects. With this we hope to support Kids First as a whole and establish standards for data sharing in clinical genomics, accelerating collaboration and facilitating robust disease gene discovery.

我们建议继续提供数据生成和处理活动，以丰富基因组数据 推动儿科疾病研究的资源是成功计划的关键要素。 表型良好的患者及其家属的高质量基因组序列数据的收集和 以直观的方式向研究界提供数据；以及将遗传数据与 该程序背景下的表型信息以及与其他大数据资源的比较。 最终目标是收集结构性出生缺陷和儿科疾病背后的完整基因目录 癌症，并利用这些信息更好地了解疾病机制、诊断 机会和治疗方向。 我们建议继续将布罗德研究所作为儿童优先测序中心，就像我们为 过去三年该计划以及我们为支持其他大型旗舰 NIH 基因组所做的努力 我们的中心带来的领域专业知识是高吞吐量数据生成、处理和分析， 以及实现“儿童优先计划”目标所需的疾病基因发现。 我们将在选定的样本上应用深度、高质量的全基因组测序数据。我们将保持灵活性。 在接下来的三年里密切合作并满足选定的 X01 调查员的需求和兴趣。 一年期间，我们可以提供多达 25,000 个样本，突破了新数据类型和更低数据类型的界限 我们可以灵活地混合队列类型，无论是三人组（针对结构性出生缺陷）还是四人组。 （在癌症研究中）我们将与 X01 研究者合作引入新的数据类型，例如 RNASeq 或 Long 适当时阅读排序。我们将参与这些数据类型及其整体的评估。 对计划的发现和科学产出的影响 我们中心的一个关键特点是我们实施了强大的变异评估分析框架 和疾病基因发现，这是建立在广泛研究人员在统计遗传学领域世界领先地位的基础上的， 功能注释、临床变异解释以及获取外显子组和基因组数据 Broad 测序了数十万个样本，这使我们能够构建系统化的流程。 基因发现将免费提供给“儿童优先”计划，并生成和处理数据。 以一致的方式，我们可以将 Kids First 数据无缝集成到我们的分析框架中。 在儿科研究界针对的疾病中，需要自信地发现致病基因 我们将与 Kids First Data Resource 合作，汇总世界各地的案例。 以多种方式集中，确保该计划与其他大型资源保持一致 我们希望以此来支持“儿童优先”并建立数据标准。 共享临床基因组学，加速合作并促进强大的疾病基因发现。