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: 9888328
• 负责人: JILL Allison HOLLENBACH
• 金额: $ 37.74万
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888328
• 关键词: 6p21; Address; Adopted; Alleles; Base Sequence; Basic Science; Biological Models; Bone Marrow; Chromosome 19; Chromosome 6; Clinical; Clinical Data; Clinical Research; Collection; Communities; Complex; Computer software; Consensus Sequence; Coupled; Coupling; Data; Data Analyses; Data Reporting; Data Set; Data Storage and Retrieval; Development; Disease; Docking; Exhibits; Fast Healthcare Interoperability Resources; Future; Future Generations; GB virus C; Gene Structure; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomic Segment; Genotype; Goals; Gold; Guidelines; HLA Antigens; Haplotypes; Health; Healthcare Systems; Human; Human Chromosomes; Human Genome; Immunogenomics; Immunoglobulins; Individual; Killer Cells; Language; Medical; Medical Research; Methods; Modernization; Nomenclature; Organ Transplantation; Output; Patients; Play; Population; Population Genetics; Publications; Receptor Gene; Reporting; Reproducibility; Research; Resources; Rest; Role; Science; Services; Single Nucleotide Polymorphism; Software Tools; Solid; Standardization; Statistical Data Interpretation; Study models; System; Transplant-Related Disorder; Variant; Work; analytical tool; bench to bedside; clinical application; clinical practice; data analysis pipeline; data exchange; data format; data management; data pipeline; data standards; data tools; design; experience; genetic analysis; genetic association; genomic data; health disparity; human data; improved; next generation; open source; operation; portability; precision medicine; programs; receptor; skills; tool; web services

PROJECT SUMMARY/ABSTRACT The goal of the proposed work is to further develop and integrate our software for the analysis, collection, exchange and storage (ACES) of all current and future immunogenomic data. The Human Leukocyte Antigen (HLA) region on human chromosome 6p21 is the most medically important region of the human genome. In the most successful application of precision medicine to date, 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 extensive genetic variation of these immunogenomic loci in human populations also makes them model systems in health disparities research. However, 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. Recognizing the need to consolidate the data and standardize data analysis in such a broad field, we have developed our Push Immunogenomics to the Next Generation (PING) data-generation system, Toolkit for Immunogenomic Data Exchange and Storage (TIDES) data-management platform, and our Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) data-analysis pipeline for highly polymorphic genomic data. When coupled with our Genotype List Service, Histoimmunogenetic Markup Language and Minimum Information for Reporting Immunogenomic NGS Genotyping reporting data-exchange standard, our ACES systems will represent a significant advance toward the goal of completely integrated exchange and storage of immunogenomic data. To extend our work of the prior period, we will (1) further develop the TIDES platform as the hub that integrates these systems, services and standards, centralize consensus sequence as the primary data type in immunogenomic research and clinical practice, and develop a service for gene feature enumeration (GFE) that describes HLA and KIR polymorphism by acknowledging underlying gene structure. To facilitate analysis of these data for research and clinical applications, we will (2) extend our BIGDAWG pipeline to handle new data input formats, incorporate new analyses, and export new data formats. BIGDAWG will be adapted as TIDES' primary analysis partner, and will directly, seamlessly accept TIDES outputs. Our tools are designed to maximize the ongoing utility of immunogenomic data for clinical and basic research science. As leaders in the immunogenomics field, we are uniquely suited to address the critical unmet need for standardized, robust ACES of immunogenomic data. The capacity of the systems described here to take these complex, highly polymorphic and medically important data along a complete pipeline from data generation through high-level statistical analysis will be a significant milestone toward the goal of “bench to bedside” precision medicine.

项目总结/摘要 拟议工作的目标是进一步开发和整合我们的软件，用于分析，收集， 所有当前和未来的免疫基因组学数据交换和存储（ACES）。人类白细胞抗原 (HLA)人类染色体6p 21上的区域是人类基因组中最重要的医学区域。在 迄今为止，精确医学最成功的应用是，骨骼需要HLA基因型的匹配， 骨髓和实体器官移植。HLA分子与杀伤细胞有功能性相互作用 免疫球蛋白样受体（KIR）分子，也被认为在移植和免疫调节中发挥关键作用。 疾病这些免疫基因组位点在人群中的广泛遗传变异也使它们 健康差异研究中的模型系统。然而，由于这些免疫基因组学数据已经被 使用各种各样的方法和不同的命名系统生成，交叉研究数据 兼容性仍然是该领域的一个重要和削弱性的限制。认识到需要 为了在如此广泛的领域中整合数据并标准化数据分析，我们开发了我们的Push 下一代免疫基因组学（PING）数据生成系统，免疫基因组数据工具包 数据交换和存储（TIDES）数据管理平台，以及我们的桥接免疫基因组数据分析 针对高度多态性基因组数据的工作流缺口（BIGDAWG）数据分析管道。再加上 我们的基因型列表服务，组织免疫标记语言和报告的最低信息 免疫基因组学NGS基因分型报告数据交换标准，我们的ACES系统将代表 这是实现免疫基因组学数据完全集成交换和存储目标的重大进展。 为了延续我们前期的工作，我们将（1）进一步开发TIDES平台，作为整合 这些系统、服务和标准将共识序列集中为主要数据类型， 免疫基因组学研究和临床实践，并开发一种基因特征计数（GFE）服务， 通过了解潜在的基因结构描述HLA和KIR多态性。为便利分析 这些数据用于研究和临床应用，我们将（2）扩展BIGDAWG管道以处理新数据 输入格式、合并新的分析以及导出新的数据格式。BIGDAWG将被改编为TIDES 主要分析合作伙伴，并将直接，无缝地接受TIDES输出。我们的工具旨在 最大限度地提高免疫基因组学数据在临床和基础研究科学中的持续效用。作为领导者， 免疫基因组学领域，我们是唯一适合解决关键的未满足的需求，标准化，强大的 免疫基因组学数据的ACES。这里描述的系统的能力，采取这些复杂的，高度 多态和医学上重要的数据沿着从数据生成到高级 统计分析将是实现“从实验台到床边”精确医疗目标的一个重要里程碑。