MOLECULAR SIGNATURES OF IMMUNE RESPONSE TO VACCINATION

为了确定成功接种疫苗的关键决定因素，至关重要的是确定全球 相关免疫反应的签名。我们建议通过以下方式识别这些签名 高通量信使核糖核酸技术、蛋白质组学技术和 计算工具。 基因组学核心的目标是提供高通量测序和微阵列设施 疫苗联盟的调查人员。测序设施将可用于分析cdna文库， 其将被用于定制阵列构造。微阵列设备将用于分析 不同免疫细胞群体在不同刺激条件下的mRNA表达谱。 蛋白质组学核心的目的是协助中心研究人员对蛋白质组进行定量定义 免疫细胞对免疫作出反应时的变化。分析的重点是描述 免疫细胞(T和B淋巴细胞和树突状细胞)蛋白质组内的特殊变化，以及 病人的血清。这些研究旨在阐明膜糖蛋白的变化(共刺激和 贩运)、胞质磷蛋白(信号转导)和核蛋白(基因表达和 细胞分化)。血清糖蛋白将在免疫后的早期和后期进行定量。 找出与有效记忆免疫形成相关的体液因素 回应。 生物信息学核心将提供用于以标准化格式存储数据的中央储存库， 它将允许分析、集成和共享来自各种不同技术的数据 调查人员。核心将提供软件工具，使研究人员能够探索数据，使 数据集之间的比较，用特定假设询问数据集，以及全局询问 数据集，以识别不同数据源之间的新模式和关联。工具也将是 被提供来同时可视化和集成多维数据集。这些计算工具 对于从单个分子和分子之间的关系中提取有意义的洞察是必不可少的 对接种疫苗的系统性免疫反应。

In order to define the critical determinants of successful vaccination, it is crucial to identify the global signatures of the associated immune response. We propose to identify these signatures through the application of a combination of high-throughput mRNA technologies, proteomic technologies, and computational tools. The aim of the genomics core is to provide high-throughput sequencing and microarray facilities for investigators in the vaccine consortium. Sequencing facilities will be available to analyze cDNA libraries, which will be utilized for customized array construction. The microarray facilities will be used for analysis of mRNA expression profiles in populations of different immune cells under various stimulatory conditions. The aim of the proteomics core is to assist the center investigators in quantitatively defining proteomic changes in immune cells as they respond to immunization. The focus of the analyses is to characterize specific changes within the proteomes of immune cells (T and B lymphocytes and dendritic cells), and within patients' sera. These studies aim to elucidate changes in membrane glycoproteins (co-stimulation and trafficking), cytosolic phosphoproteins (signal transduction), and nuclear proteins (gene expression and cellular differentiation). Serum glycoproteins will be quantitated at early and later time points postimmunization to identify humoral factors that correlate with the development of an effective memory immune response. The bioinformatics core will provide a central repository for the storage of data in a standardized format, which will permit data from a variety of different techniques to be analyzed, integrated and shared between investigators. The core will provide software tools to enable researchers to explore the data, make comparisons between data sets, to interrogate data sets with specific hypotheses, and to globally interrogate data sets to identify novel patterns and associations among disparate data sources. Tools also will be provided to simultaneously visualize and integrate multi-dimensional data sets. These computational tools will be essential for extracting meaningful insight from the relationships between individual molecules and systemic, immune responses to vaccination.