GMKF competing renewal

摘要 我们建议继续提供数据生成和处理活动， 基因组数据资源，以推动儿科疾病的研究。成功计划的关键要素将 提供高质量的基因组序列数据的良好表型的患者和他们的家庭; 以直观的方式收集数据并使研究界能够获得数据;以及 在该计划的背景下整合遗传数据与表型信息，并与 其他大数据资源。最终目标是收集一个完整的基因目录， 结构性出生缺陷和儿科癌症的基础，并使这些信息的使用，以更好地 了解疾病机制、诊断时机和治疗方向。 我们建议继续作为一个孩子第一测序中心在布罗德研究所，因为我们已经做了 在过去的六年里，我们一直在支持该项目，正如我们在支持其他大型旗舰NIH项目时所做的那样， 基因组计划。我们的中心带来的领域专长是高吞吐量数据生成、处理 和分析，以及疾病基因的发现，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。我们将 灵活地密切合作，并满足选定X01研究者的需求和兴趣。超过 在接下来的三年里，我们可以提供多达23,000个样本， 数据类型和更低的成本。我们可以灵活地混合队列类型，无论它们是基于三人组（对于 结构性出生缺陷）或四头畸形（在癌症研究中）。我们将与X01调查人员合作， 互补数据类型，如RNASeq或长读段测序。我们将 参与评估这些数据类型及其对发现和科学产出的总体影响 的计划。 我们中心的一个主要特点是我们实施了一个强大的分析框架， 评估和疾病基因发现，这是建立在广泛的研究人员的世界领先的作用， 统计遗传学、功能注释和临床变异解释以及外显子组访问 以及布罗德测序的数十万个样本的基因组数据。这使我们能够 建立一个系统的基因发现管道，将免费提供给儿童第一计划。 通过以一致的方式生成和处理数据，我们可以无缝集成Kids First 我们的分析框架。对于儿科研究界针对的许多疾病， 要有信心地发现致病基因，就需要将世界各地的病例集中起来。 我们将以各种方式与Kids First数据资源中心合作，以确保该计划 与其他大型资源生成项目保持一致。我们希望以此来支持孩子们 首先作为一个整体，建立临床基因组学数据共享标准，加速合作 并促进稳健的疾病基因发现。

ABSTRACT 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 six 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 23,000 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 generate complementary 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.