DNA Sequencing Support for the eMERGE Network

电子病历和基因组学（eMERGE）网络的eMERGE第三阶段：中央基因组 测序和基因分型设施“（RFA-HG-027），将提供最先进的能力， eMERGE患者关键基因和基因组区域的DNA序列。这项工作将在 在贝勒DNA诊断实验室，人类基因组测序的合作努力， 中心（HGSC）和分子和人类遗传学系（DMHG），合并 这两个小组的互补专业知识，使CAP和CLIA认证的临床测序测试。一 Partners-Broad的互补协作小组将平行工作，以实现类似的目标。一个 所附文件“BCM-Partners-Broad eMERGE测序核心合作计划”详细说明了 协作 在2010年，将对约100个选定基因的完整序列进行分析，然后对假定的变异进行验证。 最初通过定制的DNA捕获面板进行，可能会引入替代方法， 方案成熟。在这份修订后的提案中，将在整个过程中分析总共12，500个样本， 项目（第一年2，700人;此后每年3，267人）。如原始申请中所述， 方法将基于NimbleGen DNA捕获技术和Illumina DNA测序 HGSC开创的程序将在2013年协调捕获面板的内容 由哈佛的海蒂雷姆博士的小组设计和使用的小组，确保简单但强大的交叉 平台之间的联系。此外，我们将利用编码变体解释和报告， 自动向eMERGE参与者报告。将提供用于验证关键变体的桑格方法。 目标的一个关键修改将是扩大分布式计算的使用，使所有人都能轻松访问 项目数据来自多个（可能是所有）站点。将从测序样本中收集数据， 以统一的格式安全存储。这些数据、解释结果和临床报告将 合格用户可通过安全访问和传输协议访问。eMERGE数据共享将允许 通过eMERGE调查员网络快速、安全和公平地传输数据和信息， 将创造一个环境，随着新工具和知识的出现， available. 为了促进进展，两个中心将成立四个工作组：1.试验设计; 2. 测序生产; 3.医生界面; 4.数据共享。

This Electronic Medical Records and Genomics (eMERGE) Network ‘eMERGE Phase III: Central Genome Sequencing and Genotyping Facility’ (RFA-HG-027), will provide state-of-the-art capabilities for the generation of the DNA sequence of key genes and genomic regions in eMERGE patients. The work will be performed within the Baylor DNA Diagnostic Laboratories, a collaborative effort of the Human Genome Sequencing Center (HGSC) and the Department of Molecular and Human Genetics (DMHG), merging the complementary expertise of both groups to enable CAP and CLIA certified clinical sequencing tests. A complementary, collaborative group at Partners-Broad will work in parallel to achieve similar goals. An appended document ‘BCM-Partners-Broad eMERGE Sequencing Core Collaboration Plan’ details the collaboration. At BCM, the complete sequences of ~100 selected genes, followed by validation of putative variants, will be carried out initially via a custom DNA capture panel, with alternate methods potentially introduced as the program matures. In this revised proposal, a total of 12,500 samples will be analyzed over the course of the project (2,700 in year one; 3,267 per year, thereafter) at BCM. As described in the original application, the methods will be based upon the NimbleGen DNA capture technology and Illumina DNA sequencing procedures that were pioneered at the HGSC. The content of the capture panel at BCM will be coordinated with the panel designed and utilized by Dr. Heidi Rehm’s group at Harvard, ensuring simple but robust cross reference between platforms. Further, we will utilize the Codified variant interpretation and reporting to provide automated reports to eMERGE participants. Sanger methods for validation of key variants will be available. A key modification of the Aims will be to expand the use of distributed computing to enable facile access to all project data from multiple (and potentially all) sites. Data will be collected from sequenced samples and securely stored in a single harmonized format. These data, interpretation results and clinical reports will be accessible to qualified users via secure access and transfer protocols. The eMERGE data commons will allow for rapid, secure and equitable transfer of data and information across the eMERGE investigator network and will create an environment for real-time reinterpretation of results as new tools and knowledge become available. To facilitate progress, four working groups from the two Centers will be formed: 1. Assay Design; 2. Sequencing Production; 3. Physician Interface; 4. Data Commons.