University of Washington (UW) Mendelian Genomics Data Coordinating Center

项目摘要 尽管在了解估计超过10，000种的遗传基础方面取得了重大进展， 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 孟德尔疾病及其潜在的遗传原因。在中心成功的基础上， 孟德尔基因组学通过使用进一步的技术，方法和数据共享创新，NHGRI是 建立一个新的孟德尔基因组学研究联盟作为数据协调中心， 财团，我们建议进一步发现和孟德尔条件的表征，实现 四大目标。(1)管理由生物技术研究所生成或收集的分子和表型数据的发布 联盟的研究中心，具有半自动化和可扩展的质量控制程序， 根据协作建立的标准和要求验证传入数据。我们将促进数据 在联盟和更广泛的科学界内共享，确保管理的数据 提交到适当的存储库，包括AnVIL，ClinVar和Matchmaker Exchange。(2)支持 通过联盟网站突出项目进展和发现的项目外展， 使研究人员、临床医生和家庭之间能够建立联系。我们还将监督教育，培训， 和指导机会。(3)协调联合体的后勤工作，包括组织虚拟 以及为所有联盟范围内的活动提供面对面会议和行政支持。(4)监督一个 机会基金，在联盟的第2-5年每年管理多达5个奖项，以支持新的和 对候选变体进行功能性随访的可扩展方法。为了实现这四个主要目标，我们 提出创新方法，包括利用新兴的基于云的存储系统， 分析人类基因数据，整合国际数据共享标准，确保数据 可查找、可访问、可互操作和可重用（FAIR）。此外，我们还提供独特的专业知识， 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遗传学等领域 我们的应用基于13年的成功经验和专业知识， 作为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 和协调该财团，我们将有助于产生的好处，确定孟德尔遗传基础， 支持诊断、治疗和进一步描述综合征的条件。进一步的公共卫生效益将 通过对孟德尔疾病的生物学见解，也促进了我们对相关共同， 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.