GMKF competing renewal

摘要 我们建议继续提供数据生成和处理活动，以丰富 推动儿科疾病研究的基因组数据资源。一个成功计划的关键要素是 提供表型良好的患者及其家属的高质量基因组序列数据； 以直观的方式收集和获取数据；以及 将遗传数据与表型信息结合在这一方案的背景下，并与 其他大数据资源。最终目标是组装一个完整的基因目录， 结构性出生缺陷和儿童癌症的潜在原因，并使这些信息的使用能够更好地 了解疾病机制、诊断机会和治疗方向。 我们建议继续在布罗德研究所作为儿童第一测序中心，就像我们已经做的那样 在过去的六年里，我们一直在支持NIH的其他大型旗舰项目 基因组计划。我们的中心带来的领域专业知识是高通量数据的生成、处理 和分析，以及疾病基因发现，以满足儿童优先计划的目标。 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。我们会的 灵活地密切合作，并满足选定的X01调查人员的需求和兴趣。完毕 在接下来的三年里，我们可以提供多达23,000个样品，推动新的 数据类型和更低的成本。我们可以灵活地混合使用不同的队列类型，无论它们是基于三人组的(对于 结构性出生缺陷)或四联征(在癌症研究中)。我们将与X01调查人员合作，生成 补充数据类型，如RNAseq或长读取序列(如果合适)。我们会 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 计划的一部分。 我们中心的一个主要特点是我们实施了一个强大的变种分析框架 评估和疾病基因发现，这是建立在远大调查公司在全球领先的 统计遗传学、功能注释、临床变异解释以及访问外显子组 布罗德大学对数十万个样本的基因组数据进行了测序。这使我们能够 建立一个系统的基因发现管道，将免费提供给儿童优先计划。 通过以一致的方式生成和处理数据，我们可以首先提供Kids的无缝集成 将数据输入我们的分析框架。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，将需要在世界各地的各个中心汇总病例。 我们将以各种方式与儿童第一数据资源中心合作，以确保该计划 与其他大型资源生产项目很好地结合在一起。有了这一点，我们希望支持孩子们 首先作为一个整体，建立临床基因组学数据共享的标准，加快协作 并促进强大的疾病基因发现。

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.