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

项目摘要/摘要 拟议工作的目标是进一步开发和集成我们的软件，用于分析、收集、 交换和存储(ACE)所有当前和未来的免疫基因组数据。人类白细胞抗原 人类染色体6p21上的(HL A)区是人类基因组中最重要的医学区域。在 迄今为止最成功的精确医学应用，需要对骨骼进行人类白细胞抗原基因分型。 骨髓和实体器官移植。人类白细胞抗原分子与杀伤细胞具有功能性相互作用 免疫球蛋白样受体(KIR)分子，也被认为在移植和 疾病。这些免疫基因座在人类群体中的广泛遗传变异也使它们 健康差距研究中的模型系统。然而，因为这些免疫基因组数据已经被 使用各种方法并在不同的命名系统下生成交叉研究数据 兼容性仍然是该领域的一个重要和令人衰弱的限制。认识到有必要 在如此广阔的领域整合数据和规范数据分析，我们已经发展了我们的推动力 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 交换和存储(DEDS)数据管理平台，以及我们的桥接免疫基因组数据分析 高度多态基因组数据的工作流差距(BIGDAWG)数据分析管道。当与 我们的基因类型列表服务、组织免疫遗传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ACE系统将代表一个 朝着免疫基因组数据的完全集成交换和存储的目标取得重大进展。 为扩展前期工作，我们将(1)进一步发展潮汐平台作为集成的枢纽 这些系统、服务和标准将共识序列集中为 免疫基因组学研究和临床实践，并开发基因特征枚举(GFE)服务 通过了解潜在的基因结构描述了人类白细胞抗原和KIR基因的多态性。为了便于分析 这些数据用于研究和临床应用，我们将(2)扩展我们的BIGDAWG渠道以处理新数据 输入格式、合并新分析和导出新数据格式。BIGDAWG将被改编为潮汐 主要分析合作伙伴，并将直接、无缝地接受潮汐输出。我们的工具旨在 最大限度地发挥免疫基因组数据对临床和基础研究科学的持续效用。作为世界上的领导者 作为免疫基因组学领域的一员，我们非常适合满足标准化、健壮的关键需求 免疫基因组数据的王牌。这里描述的系统的能力可以将这些复杂的、高度 从数据生成到高级的完整管道中的多态和医学上重要的数据 统计分析将是迈向“从床到床”精准医学目标的一个重要里程碑。

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.