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

项目摘要 人类染色体6p21上的人类白细胞抗原（HLA）区域是医学上最重要的区域 人类基因组。超过100种感染性、自身免疫性和药理学疾病表型和癌症 与HLA的遗传变异有关，骨髓和骨髓细胞需要HLA基因型的匹配， 实体器官移植HLA分子与杀伤细胞免疫球蛋白样蛋白具有功能性相互作用 受体（KIR）分子，也被认为在移植和疾病中发挥关键作用。的基因 编码这些分子是高度多态性的，并且相对于其它分子显示出广泛的结构变异。 基因组区域。认识到需要整合来自广泛领域的复杂数据，在先前的项目中， 在此期间，我们开发了一套工具和程序，用于标准化的分析，收集，交换和 所有当前和未来免疫基因组学数据的ACES存储。这些工具有助于填补基因组数据的空白- 管理和分析工具，主要设计用于单核苷酸多态性（SNP） 和全基因组和全外显子组序列（WG/ES）数据，并不支持高度多态性 以免疫基因组位点和其他高度多态性遗传系统为特征的遗传数据。我们 标准和工具已被免疫基因组学界广泛采用，但仍有一个紧迫的问题， 和未满足的需要，整合，易于使用，临床级的工具，统一免疫基因组基因型，SNP和 WG/ES数据，同时预测未来的基因组数据格式。在过去的项目期间，我们已经取得了 在开发这些工具和资源方面取得实质性进展，这些工具和资源旨在最大限度地 免疫基因组学数据在临床和基础研究科学中的持续效用。在拟议的项目期间， 我们将推进这些工具的开发，扩大其范围，提高易用性， 它们的可用性以及与电子病历（EMR）系统的互操作性， 这些高度复杂的数据集可用于转化医学。我们将扩大 我们的工具和服务的实用性，以适应额外的数据类型和分析方法，以及 整合各种方法。在我们开发支持HLA传输的基础设施的基础上再接再厉 使用HL7 FHIR资源收集数据，我们将努力将这些资源整合到我们的数据管理工具中 管道。最后，我们将在为支持聚合和标准化而开发的基础设施上构建 在COVID-19背景下分析HLA数据，以支持其他数据类型和疾病表型， 免疫基因组疾病相关研究。通过整合这些资源以及其他工具和服务， 已经开发出，并使他们能够产生FHIR信息，这些免疫基因组学的产物， ACES资源可供研究人员和卫生系统使用， 了解人类健康中的免疫基因组学，并促进转化医学的应用。

PROJECT SUMMARY The Human Leukocyte Antigen (HLA) region on human chromosome 6p21 is the most medically important region of the human genome. Over 100 infectious, autoimmune and pharmacological disease phenotypes and cancers are associated with genetic variation of HLA, and matching of HLA genotypes is required for bone marrow and solid organ transplantation. HLA molecules have functional interactions with Killer cell Immunoglobulin-like Receptor (KIR) molecules, also recognized to play critical roles in transplantation and disease. The genes encoding these molecules are highly polymorphic and display extensive structural variation relative to other genomic regions. Recognizing the need to consolidate complex data from a broad field, in the prior project periods we developed a suite of tools and programs for the standardized analysis, collection, exchange and storage (ACES) of all current and future immunogenomic data. These tools serve to fill gaps in genomic data- management and analysis tools, which are primarily designed for use with single nucleotide polymorphism (SNP) and whole-genome and whole-exome sequence (WG/ES) data, and do not support the highly polymorphic genetic data characterized by the immunogenomic loci and other highly polymorphic genetic systems. Our standards and tools have been widely adopted by the immunogenomics community, but there remains an urgent and unmet need for integrated, easy-to use, clinical-grade tools that unify immunogenomic genotype, SNP and WG/ES data, while anticipating future genomic data formats. In the previous project periods, we have made substantial progress on the development of these tools and resources, which are designed to maximize the ongoing utility of immunogenomic data for clinical and basic research science. In the proposed project period, we will advance the development of these tools, expanding their scope and improving ease of use, centralizing their availability and enabling interoperability with electronic medical record (EMR) systems, and making them available adjacent to these highly complex datasets for application in translational medicine. We will expand the utility of our tools and services to accommodate additional data types and analytical methods, as well as integrating across methods. Building on our development of an infrastructure to support transmission of HLA data using HL7 FHIR resources, we will work to incorporate these resources into our data management tools and pipeline. Finally, we will build on an infrastructure developed to support aggregation and standardized analysis of HLA data in the context of COVID-19 to support additional data types and disease phenotypes for immunogenomic disease association studies. By integrating these resources, and other tools and services we have developed, and empowering them to generate FHIR messages, the products of these immunogenomic ACES resources can be made available and accessible to researchers and within health systems, improving our understanding of immunogenomics in human health and facilitating application for translational medicine.