Integrated Exchange & Storage of Current and Future-Generation Immunogenomic Data

描述（由申请人提供）：拟议工作的目标是进一步开发和扩展我们的程序和方案的功能，用于管理和交换人类白细胞抗原（HLA）和杀伤细胞免疫球蛋白样受体（KIR）基因的遗传数据。这些基因对免疫力至关重要，对人类健康至关重要，并构成具有非常高水平的序列和结构变异的复杂遗传系统。由于这些免疫基因组学数据是使用多种方法和不同的命名系统生成的，因此交叉研究数据的兼容性仍然是该领域的一个重要和削弱性的限制。建议的工作的关键要素是整合的系统和标准，我们已经开发了与现有的公共资源的HLA和KIR基因系统，使HLA和KIR数据的可重复性和易于组合的分析。为了实现这一目标，我们将（1）扩展和完善我们的免疫基因组学数据交换和存储工具包（TIDES）和将免疫基因组学推向下一代（PING）软件。我们将通过扩展KIR基因座的功能，扩展部署选项，扩展搜索和导出能力，改进用户界面，开发新的算法用于我们新的基因型列表（GL）字符串数据记录格式，以及更好地将TIDES与现有的分析软件集成来改进TIDES。我们将自动化我们的PING管道，将其功能扩展到HLA II类位点，并将PING与TIDES集成;（2）将PING，TIDES和我们的GL服务与现有的公共注册表，工具和数据库集成。我们将调整PING以接受来自NCBI序列读取档案（SRA）和基因型和表型数据库（dbGaP）的下一代测序（NGS）读取数据，并使用NCBI MHC数据库（dbMHC）SBT输入工具生成HLA和KIR基因型。我们将开发一个LiftOver工具来跨多个参考数据库版本管理GL字符串。我们将开发一个HL 7消息传递系统，该系统集成了GL字符串、GL服务统一资源标识符（URI）和基因检测注册中心（GTR）URI，允许HLA和KIR分型结果的标准交换。我们将与NCBI合作，使这些新的服务可供使用，并将发布所有工具作为免费的开源软件。通过以这种方式促进免疫基因组学数据管理的便利性，我们将极大地增加当前和未来数据资源的价值。

DESCRIPTION (provided by applicant): The goal of the proposed work is to further develop and extend the functionality of our programs and protocols for the management and exchange of genetic data for the Human Leukocyte Antigen (HLA) and Killer cell Immunoglobulin-like Receptor (KIR) genes. These genes are central to immunity and critically important for human health, and constitute complex genetic systems with extraordinarily high levels of sequence and structural variation. Because these immunogenomic data have been generated using a wide variety of methods and under different nomenclature systems, cross-study data compatibility has remained an important and debilitating limitation to the field. The key element of the work proposed is the integration of the systems and standards that we have developed with existing public resources for the HLA and KIR gene systems to enable both reproducible and easily combined analyses of HLA and KIR data. To accomplish this, we will (1) expand and refine our Toolkit for Immunogenomic Data Exchange and Storage (TIDES) and Push Immunogenomics to the Next Generation (PING) software. We will improve TIDES by extending functionality for the KIR loci, expanding deployment options, expanding search and export capacity, refining the user interface, developing new algorithms for use with our novel Genotype List (GL) String data recording format, and better integrating TIDES with extant analytical software. We will automate our PING pipeline, extend its functionality to HLA class II loci, and integrate PING with TIDES; and (2) integrate PING, TIDES, and our GL Service with existing public registries, tools and databases. We will adapt PING to accept next generation sequencing (NGS) read data from the NCBI Sequence Read Archive (SRA) and Genotype and Phenotype Database (dbGaP), and to generate HLA and KIR genotypes using the NCBI MHC database (dbMHC) SBT Input tool. We will develop a LiftOver tool to manage GL Strings across multiple reference database releases. We will develop an HL7 messaging system that integrates GL Strings, GL Service Uniform Resource Identifiers (URIs) and Genetic Testing Registry (GTR) URIs, allowing the standard exchange of HLA and KIR typing results. We will partner with the NCBI to make these new services publically available, and will release all tools as free open source software. By facilitating ease of immunogenomic data management in this manner we will vastly increase the value of current and future data resources.