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: 10017287
• 负责人: Stacey Gabriel
• 金额: $ 733.39万
• 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/10017287
• 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