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

当前和未来一代免疫基因组数据的集成交换和存储

• 批准号: 10442226
• 负责人: JILL Allison HOLLENBACH
• 金额: $ 49.59万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442226
• 关键词: 6p21; Address; Adopted; Advanced Development; Amino Acid Motifs; Autoimmune; Basic Science; Big Data; Bone Marrow; CD94 Antigen; COVID-19; Chromosome 19; Chromosome 6; Clinical; Clinical Data; Clinical Research; Code; Collection; Communities; Complex; Computer software; Computerized Medical Record; Copy Number Polymorphism; Data; Data Analyses; Data Set; Databases; Development; Disease; Fast Healthcare Interoperability Resources; Fostering; Future; Future Generations; Genes; Genetic; Genetic Variation; Genomic Segment; Genotype; Goals; Gold; HLA Antigens; Health; Health Insurance Portability and Accountability Act; Health Status; Health system; Housing; Human; Human Chromosomes; Human Genome; Immune; Immunogenetics; Immunogenomics; Immunoglobulins; Informatics; Infrastructure; Killer Cells; Ligands; Malignant Neoplasms; Medical; Metadata; Methods; Modernization; Organ Transplantation; Pharmacology; Play; Receptor Gene; Reporting; Research; Research Personnel; Resource Development; Resources; Rest; Role; SARS-CoV-2 antigen; Science; Services; Single Nucleotide Polymorphism; Solid; Standardization; System; Systems Integration; Transplant-Related Disorder; Variant; Work; analytical method; bench to bedside; clinical phenotype; complex data; data format; data management; design; disease phenotype; electronic data; empowered; exome; experience; genetic variant; genomic data; health management; human data; human disease; improved; infrastructure development; interoperability; next generation; novel; open source; precision medicine; programs; rare variant; receptor; tool; tool development; translational applications; translational medicine; transmission process; whole genome

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.

项目摘要 人类白细胞抗原（HLA）在人类6p21上是最重要的地区 人类基因组。超过100多种感染性，自身免疫和药理学疾病表型和癌症 与HLA的遗传变异有关，HLA基因型的匹配是骨髓和 实体器官移植。 HLA分子与杀手型细胞免疫球蛋白样具有功能相互作用 受体（KIR）分子也被公认为在移植和疾病中起关键作用。基因 编码这些分子是高度多态的，相对于其他 基因组区域。在先前的项目中，认识到需要从广泛领域巩固复杂数据 时期我们开发了一套用于标准化分析，收集，交换和的工具和程序 所有当前和将来的免疫基因组数据的存储（ACE）。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） 以及全基因组和全身序列（WG/ES）数据，并且不支持高度多态 以免疫基因座和其他高度多态遗传系统为特征的遗传数据。我们的 标准和工具已被免疫基因组学社区广泛采用，但仍有紧急 以及对统一免疫基因型，SNP和 WG/ES数据，同时预测未来的基因组数据格式。在前面的项目期间，我们做了 在这些工具和资源的开发方面取得了重大进展，这些工具和资源旨在最大化 免疫基因组数据的持续实用性用于临床和基础研究科学。在拟议的项目期间， 我们将推进这些工具的开发，扩大其范围并提高易用性，集中化 它们的可用性并启用与电子病历（EMR）系统的互操作性，并使它们 这些高度复杂的数据集附近可用于转化医学。我们将扩展 我们的工具和服务的实用程序，以适应其他数据类型和分析方法以及 跨方法集成。建立在我们建立基础设施以支持HLA传播的基础上 使用HL7 FHIR资源的数据，我们将努力将这些资源纳入我们的数据管理工具 和管道。最后，我们将建立在开发的基础架构以支持聚合并标准化的基础架构的基础上 在Covid-19的背景下对HLA数据的分析，以支持其他数据类型和疾病表型 免疫基因组疾病协会研究。通过整合这些资源以及其他工具和服务，我们 这些免疫基因组的产物已经开发并授权它们生成FHIR信息 可以使研究人员和卫生系统中的ACES资源可用和访问，从而改善了我们的 了解人类健康中免疫基因组学并促进转化医学的应用。