University of Washington (UW) Mendelian Genomics Data Coordinating Center

项目总结 尽管在理解10,000多个估计的 在近几十年的孟德尔条件下，需要进一步的科学合作和发现来确定 全套孟德尔疾病及其潜在的遗传原因。在中心成功的基础上再接再厉 孟德尔基因组通过使用进一步的技术、方法和数据共享创新，NHGRI 建立一个新的孟德尔基因组研究联盟。作为此项目的数据协调中心 ，我们建议通过实现以下方法来进一步发现和刻画孟德尔条件 四个主要目标。(1)管理分子和表型数据的发布， 财团的研究中心，具有半自动和可扩展的质量控制程序，将 根据协作建立的标准和要求验证传入数据。我们将为数据提供便利 在联盟和更广泛的科学界内共享，确保经过管理的数据 提交到适当的存储库，包括Anvil、ClinVar和Matchaker Exchange。(2)配套 通过财团网站宣传计划，突出计划进展和发现，并 促进研究人员、临床医生和家庭之间的联系。我们还将监督教育、培训、 和导师的机会。(3)协调联合体的物流，包括组织虚拟 以及为财团范围内的所有活动提供面对面的会议和行政支持。(4)监管 机会基金，在财团的2-5年中每年管理最多5个奖项，以支持小说和 对候选变体进行功能跟踪的可扩展方法。为了达到这四个主要目标，我们 提出创新方法，包括利用新兴的基于云的系统进行存储和 分析人类基因数据，并整合国际数据共享标准，以确保数据 可查找、可访问、可互操作和可重复使用(公平)。此外，我们带来了独特的专业知识组合 横跨数据科学、云系统、生物统计学、生物伦理学、临床遗传学和孟德尔学派 发现给财团，我们的应用依赖于13年的成功经验和专业知识 担任7个大型遗传和生物医学项目的协调或分析中心。通过支持 在这个联盟的协调下，我们将帮助产生确定孟德尔遗传基础的好处 支持诊断、治疗和进一步描述症状的条件。进一步的公共卫生福利将 通过对孟德尔疾病的生物学见解来积累，这也促进了我们对相关常见疾病的理解， 复杂的疾病。

PROJECT SUMMARY Despite significant advances made in understanding the genetic basis of the more than 10,000 estimated Mendelian conditions in recent decades, further scientific collaboration and discovery is required to identify the full set of Mendelian diseases and their underlying genetic causes. To build on the success of the Centers for Mendelian Genomics by using further technological, methodological, and data-sharing innovations, NHGRI is establishing a new Mendelian Genomics Research Consortium. As Data Coordinating Center for this Consortium, we propose to further the discovery and characterization of Mendelian conditions by achieving four main aims. (1) Managing the release of molecular and phenotypic data generated or collected by the Consortium's Research Centers, featuring semi-automated and scalable quality control procedures that will validate incoming data against collaboratively-established standards and requirements. We will facilitate data sharing within the Consortium and the broader scientific community by ensuring that curated data are submitted to appropriate repositories including AnVIL, ClinVar, and Matchmaker Exchange. (2) Supporting program outreach through a Consortium website that highlights program progress and discoveries and enabling connections among researchers, clinicians, and families. We will also oversee education, training, and mentorship opportunities. (3) Coordinating logistics for the Consortium, including organization of virtual and in-person meetings and administrative support for all Consortium-wide activities. (4) Overseeing an Opportunity Fund, administering up to 5 awards in each of years 2-5 of the Consortium, to support novel and scalable approaches to functional follow-up on candidate variants. To achieve these four main aims, we propose innovative approaches, including leveraging emerging cloud-based systems for the storage and analysis of human genetic data and integrating international data sharing standards to ensure that data is findable, accessible, interoperable, and reusable (FAIR). Furthermore, we bring a unique blend of expertise across the fields of data science, cloud systems, biostatistics, bioethics, clinical genetics, and Mendelian discovery to the Consortium, and our application rests on 13 successful years of experience and expertise serving as Coordinating or Analysis Centers for 7 large-scale genetic and biomedical projects. Through support and coordination of this Consortium, we will help yield the benefits of identifying the genetic basis of Mendelian conditions to support diagnosis, therapy, and further delineation of syndromes. Further public health benefit will accrue via biological insights into Mendelian diseases that also advance our understanding of related common, complex diseases.