The Baylor-Hopkins Clinical Genomics Center for All of Us

贝勒-霍普金斯大学临床基因组学中心

• 批准号: 10003441
• 负责人: ERIC A. BOERWINKLE
• 金额: $ 1385.5万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-25 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10003441
• 关键词: Awareness; Biological Assay; CLIA certified; Clinical; Collaborations; Communication; Communities; Cost efficiency; Data; Environment; Genetic; Genome; Genomics; Genotype; Hereditary Disease; Individual; Medicine; Metadata; Methods; Participant; Pathogenicity; Phase; Population; Process; Protocols documentation; Public Health Schools; Reporting; Research; Sampling; Secure; Texas; United States National Institutes of Health; Universities; Validation; Variant; Work; cloud based; college; cost; experience; frontier; genomic data; human genome sequencing; innovation; member; programs; software development; tool; whole genome

The Baylor-Hopkins Clinical Genomics Center (BHCGC), incorporating the Baylor College of Medicine (BCM) Human Genome Sequencing Center (HGSC) and the Johns Hopkins University Center for Inherited Disease Research (CIDR) will perform at least 900,000 whole genome array genotype assays and 700,000 whole genome sequences with a minimum of 35-fold coverage, over five years, for the National Institutes of Health’s All of Us Program (AoU). The work will all be carried out in CAP/CLIA certified environments and will favor Illumina platforms, with a projected average cost of less than $31 per genotype and $647 per WGS, respectively. Sequencing and analyses will be performed with NIH compliant pipelines and population-aware methods applied for phasing and ancestry determination. Automated methods will identify and rank putative pathogenic or likely pathogenic variants for every participant, and make available the results in both ‘pre-reports’ and in a searchable environment, assisting selection of a subset of individuals for Clinical Validation. Signed, Clinical Reports will be generated for up to six thousand participants per year, leveraging BCM’s deep experience in genetic interpretation. The partnership will maintain a secure cloud Baylor-Hopkins AoU Portal (BHAoU Portal) to manage sample tracking and to distribute all data, with symmetric access to BHCGC and AoU DCR and GRC members. Data flow and population level analyses will be overseen by partners at the University of Texas School of Public Health (UTSPH), DNAnexus will facilitate the cloud-based data communication and a collaboration with Microsoft Research will innovate in optimized computing. A new ‘Frontiers of Interpretation’ group will work locally, and with Microsoft, for application of AI methods for variant interpretation. Approximately 300 genomes will be ‘upgraded’ in quality with a battery of with other sequencing methods, in the first year, to determine the impact on Clinical Reporting and guide program adjustments. Pursuit of innovation for enhanced analytical value or cost efficiencies will be a priority. Direct deliverables to the AoU DRC will include sample metadata, raw and processed genomic data, variant interpretations, and preliminary and signed Clinical Reports. In addition, all protocols, tools, and software developed for the All of Us program will be made available to the program and to the broader scientific community.

贝勒-霍普金斯临床基因组中心 (BHCGC)，合并贝勒医学院 (BCM) 人类基因组测序中心 (HGSC) 和约翰霍普金斯大学遗传病中心 研究 (CIDR) 将进行至少 900,000 次全基因组阵列基因型分析和 700,000 次全基因组阵列基因型分析。 五年内，美国国立卫生研究院的基因组序列覆盖率至少达到 35 倍 我们所有人计划（AoU）。所有工作将在 CAP/CLIA 认证的环境中进行，并有利于 Illumina 平台的预计平均成本分别低于每个基因型 31 美元和每个 WGS 647 美元。 测序和分析将使用符合 NIH 标准的流程并应用群体感知方法进行 用于分阶段和血统确定。自动化方法将识别假定的致病性或可能的致病性并对其进行排序 每个参与者的致病变异，并在“预报告”和可搜索的形式中提供结果 环境，协助选择一部分个体进行临床验证。签署的临床报告将 利用 BCM 在遗传领域的丰富经验，每年为多达 6000 名参与者生成 解释。该合作伙伴关系将维护一个安全的云贝勒-霍普金斯 AoU 门户（BHAoU 门户） 管理样本跟踪并分发所有数据，并对称访问 BHCGC 和 AoU DCR 和 GRC 成员。数据流和人口水平分析将由德克萨斯大学学院的合作伙伴监督 DNAnexus 将促进基于云的数据通信和与公共卫生部 (UTSPH) 的合作 微软研究院将在优化计算方面进行创新。一个新的“解释前沿”小组将开展工作 本地并与微软合作，应用人工智能方法进行变体解释。大约300个基因组 将在第一年通过一系列其他测序方法进行质量“升级”，以确定 对临床报告和指导计划调整的影响。追求创新以提高分析价值 或者成本效率将是优先考虑的事项。直接交付给 AoU DRC 将包括样本元数据、原始数据和 处理基因组数据、变异解释以及初步和签署的临床报告。此外，所有 为“我们所有人”计划开发的协议、工具和软件将提供给该计划以及 更广泛的科学界。