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

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。一个成功的计划的关键要素将是提供 高质量的基因组序列数据的良好表型的病人和他们的家庭;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 表型信息在这个程序的上下文中，并与其他大型数据资源进行比较。的 最终目标是收集一个完整的基因目录，这些基因是结构性出生缺陷和儿科疾病的基础。 癌症，并使这些信息的使用，以更好地了解疾病的机制，诊断 机会和治疗方向。 我们建议继续作为布罗德研究所的儿童第一测序中心，就像我们为 过去三年的计划，因为我们也做了支持其他大型旗舰NIH基因组 项目我们的中心带来的领域专长是高通量数据生成、处理和分析， 和疾病基因的发现，以满足儿童第一计划的目标。 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。我们会灵活处理 密切合作并满足选定X 01研究者的需求和兴趣。在接下来的三年里- 在一年的时间里，我们可以提供多达25，000个样本，推动新数据类型的边界， 成本我们可以灵活地混合队列类型，无论是基于三胞胎（结构性出生缺陷）还是四胞胎 (in癌症研究）。我们将与X 01 Investigators合作，引入新的数据类型，如RNASeq或Long 适当时阅读测序。我们将参与对这些数据类型及其整体的评估 对项目发现和科学产出的影响 我们中心的一个主要特点是我们实施了一个强大的变异评估分析框架 和疾病基因发现，这是建立在广泛的研究人员在统计遗传学的世界领先地位， 功能注释和临床变异解释以及访问外显子组和基因组数据， 在布罗德测序了数十万个样本。这使我们能够建立一个系统的管道， 基因发现将免费提供给Kids First计划。随着数据的产生和处理 通过一致的方式，我们可以将Kids First数据无缝集成到我们的分析框架中。对于许多 在儿科研究界针对的疾病中，有信心发现致病基因将需要 全球各中心的病例汇总。我们将与儿童第一数据资源合作 以各种方式确保该计划与其他大型资源保持一致 发电项目。我们希望以此来支持儿童第一的整体，并建立数据标准 分享临床基因组学，加速合作，促进强大的疾病基因发现。

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.