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: 10889588
• 负责人: ERIC A. BOERWINKLE
• 金额: $ 1020万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10889588
• 关键词: All of Us Genome Center; All of Us Research Program; Awareness; Biological Assay; CLIA certified; Clinical; Collaborations; Communities; 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; data communication; 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学中心（Baylor-Hopkins Clinical Genomics Center，BHCGC），合并贝勒医学院（Baylor College of Medicine，BHCGC） 人类基因组测序中心（HGSC）和约翰霍普金斯大学遗传疾病中心 CIDR将进行至少90万次全基因组阵列基因型检测和70万次全基因组测序。 在五年内，美国国立卫生研究院的基因组序列覆盖率至少为35倍。 我们所有人计划（AoU）。这些工作都将在CAP/CLIA认证的环境中进行， Illumina平台，预计每个基因型和每个WGS的平均成本分别低于31美元和647美元。 测序和分析将采用符合NIH标准的管道和人群感知方法进行 用于定相和祖先确定。自动化方法将识别和排序推定的致病性或可能的 致病性变异的每一个参与者，并提供结果在这两个'预先报告'和搜索 环境，协助选择用于临床验证的个体子集。签署，临床报告将 每年为多达6000名参与者生成，充分利用了生物技术研究所在遗传学方面的丰富经验， 解释。该合作伙伴关系将维护一个安全的云Baylor-Hopkins AoU门户（BHAoU门户）， 管理样品跟踪和分发所有数据，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 公共卫生部（UTSPH），DNAnexus将促进基于云的数据通信和合作， 微软研究院将在优化计算方面进行创新。一个新的“口译前沿”小组将发挥作用 在本地，并与微软合作，应用人工智能方法进行变异解释。大约300个基因组 在第一年，将通过一系列其他测序方法在质量上进行“升级”，以确定 对临床报告的影响并指导计划调整。追求创新以提高分析价值 或者成本效率将是优先考虑的。直接交付给AoU DRC的内容将包括样本元数据、原始数据和 已处理的基因组数据、变异解读以及初步和已签署的临床报告。酒店客房经过精心 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， 更广泛的科学界。

项目成果

Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program.

• DOI: 10.1186/s13073-022-01031-z
• 发表时间: 2022-03-28
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Venner E;Muzny D;Smith JD;Walker K;Neben CL;Lockwood CM;Empey PE;Metcalf GA;Kachulis C;All of Us Research Program Regulatory Working Group;Mian S;Musick A;Rehm HL;Harrison S;Gabriel S;Gibbs RA;Nickerson D;Zhou AY;Doheny K;Ozenberger B;Topper SE;Lennon NJ
• 通讯作者: Lennon NJ

Harmonizing variant classification for return of results in the All of Us Research Program.

• DOI: 10.1002/humu.24317
• 发表时间: 2022-08
• 期刊: HUMAN MUTATION
• 影响因子: 3.9
• 作者: Harrison, Steven M.;Austin-Tse, Christina A.;Kim, Serra;Lebo, Matthew;Leon, Annette;Murdock, David;Radhakrishnan, Aparna;Shirts, Brian H.;Steeves, Marcie;Venner, Eric;Gibbs, Richard A.;Jarvik, Gail P.;Rehm, Heidi L.
• 通讯作者: Rehm, Heidi L.