Core B: Genomics and Bioinformatics Core

项目摘要：核心B 本次PPG的总主题是进一步了解von Willebrand病的分子机制 (Vwd)。每个项目将研究von Willebrand因子(VWF)的独特定量和定性方面，以及 VWD将涉及许多下一代测序(NGS)实验。因为序列数据将 需要广泛的计算、生物信息学和统计分析，我们已经建立了基因组学和 生物信息学核心，以满足这些关键需求。此外，这一核心将提供一个主要的数据存储和 为PPG和世界各地的调查人员提供数据共享功能。这一核心将有三个具体的 目标。目标1将专注于执行此PPG的所有NGS和分析。核心人员将发挥作用 在设计拟议的实验时与项目调查人员密切合作，并将提供标准分析 每个项目的编码和非编码序列。核心B将产生广泛的上游分析 VWF、RNA序列、遗传和表观遗传学全基因组序列和患者的彻底基因组分析 VWF水平低，但VWF无突变。对于此应用至关重要，核心人员还将提供 经常需要的数据解释和额外的后续数据驱动的迭代分析。这将允许 通过让计算生物学家致力于此PPG，大大提高了效率；将提供迭代 方法，因为NGS数据的分析是复杂的和实验驱动的，并将提供以下一致性 分析方法。AIM 2将保证数据的存储、管理和传输。基因组学和 生物信息学核心将利用一个新产生的基因组分析平台，该平台将是独家的 申请。该平台将成为所有原始测序数据和所有NGS的输入通道和存储库 本期PPG中的分析。所有相关的基因组结果将被转移到核心A的VELOS临床数据库中， 它们将与表型/结果数据结合在一起，以生成用户友好的界面，从而实现 PPG研究人员对表型和VWF序列变体以及其他 与VWD相关的基因。目标3将侧重于提供本地和公共数据共享。我们将确保 将原始和分析的测序数据提交到研究接受的稳定存储库 并符合NIH的数据共享政策。因此，基因组学和 生物信息学的核心将是通过互动的公共网络扩大公众对产生的基因组数据的访问 工具。在PPG的最后一年内，我们将创建一个具有用户友好界面的公共网站， 启用对多个VWF序列变体、VWD涉及的其他基因和表型数据集的查询 同时。最终，核心B代表了基因组和生物信息学数据流的中心管道 因此，这一PPG对进一步了解VWD的遗传学基础具有重要意义。

PROJECT SUMMARY: CORE B The overall theme of this PPG is to further understand the molecular mechanisms of von Willebrand Disease (VWD). Each Project will study unique quantitative and qualitative aspects of von Willebrand factor (VWF) and VWD which will involve many next-generation sequencing (NGS) experiments. Since the sequence data will require extensive computational, bioinformatic and statistical analyses, we have established a Genomics and Bioinformatics Core to serve these critical needs. In addition, this Core will provide a major data-storage and data-sharing function for both this PPG and for investigators worldwide. This Core will have three Specific Aims. Aim 1 will focus on performing all the NGS and analysis for this PPG. The Core personnel will work closely with Project investigators in the design of proposed experiments, and will provide standard analysis of both coding and noncoding sequences for each project. Core B will produce extensive upstream analyses of VWF, RNA seq, genetic and epigenetic genome wide sequences and thorough genomic analyses of patients with low VWF levels but no mutations in VWF. Critical to this application, the Core personnel will also provide data interpretation and additional follow-up data-driven iterative analyses as are often required. This will permit major increase in efficiency by having computational biologists dedicated to this PPG; will offer an iterative approach since analysis of NGS data is complex and experiment driven and will provide consistency regarding analytic approaches. Aim 2 will guarantee data storage, management and transfer. The Genomics and Bioinformatics Core will utilize a newly generated genomic Analytic Platform, which will be exclusive to this application. This platform will be the input conduit and repository for all raw sequencing data and for all NGS analyses in this PPG. All relevant genomic results will be transferred to the Velos clinical database in Core A, where they will be incorporated with phenotype/outcome data to generate a user-friendly interface that enables the simultaneous queries by PPG investigators of phenotype and VWF sequence variants, as well as other genes involved in VWD. Aim 3 will be focused on providing local and public data sharing. We will ensure that raw and analyzed sequencing data are submitted to stable repositories that are accepted by the research community and in accordance with NIH Data Sharing policy. Therefore, a major goal of the Genomics and Bioinformatics Core will be to expand public access to the generated genomic data by interactive public web tools. Within the last year of the PPG we will generate a public web site with a user-friendly interface that enables queries on multiple VWF sequence variants, other genes involved in VWD, and phenotype datasets simultaneously. Ultimately Core B represents a central conduit for genomic and bioinformatics flow of data of this PPG therefore contributing significantly to further understanding the genetics basis of VWD.