Core B - Genomics Core

项目摘要 登革病毒感染的先天免疫识别触发抗病毒免疫应答;然而， 关于病毒如何调节这些措施或这些反应如何影响登革热病毒的信息很少 （DENV）疾病发病机制和免疫。系统生物学方法旨在破译复杂的 登革病毒与宿主基因和途径之间的相互作用需要精确的高通量测量 以及全面的数据集和模型。这一重债穷国倡议的目的是利用最近取得的进展， 人类先天免疫系统早期状态的人类免疫特征分析方法 在DENV感染之后以及针对该传染病的疫苗接种之前和之后。的目标 基因组学核心是提供一个中央知识库和资源，以确定人类免疫库 并通过使用高通量测序开发疾病和疫苗反应的预测因子， 生物信息学有助于在充分表征的人类队列中研究人类免疫力。其他 HIPC研究人员将使用这些信息来获得人类免疫谱或疾病特征， 已知登革热免疫状态的自然获得性感染（项目1）、疫苗应答性和人 攻毒研究（项目2），或用不同毒力的DENV毒株离体感染DENV（项目3）。 人类免疫谱数据的网络分析将鉴定RNAi敲低的途径和基因， 确定调控网络的扰动如何影响DENV感染期间的宿主反应。 这些研究是重债穷国倡议总体目标的关键，即利用高通量系统生物学方法， 创建分子签名，将定义与免疫系统相关的人类免疫反应谱， 登革热病毒感染或疫苗接种的结果。

PROJECT SUMMARY The innate immune recognition of dengue virus infection triggers antiviral immune responses; however, there is little information about how the virus regulates these measures or how these responses affect dengue virus (DENV) disease pathogenesis and immunity. System biology approaches aimed at deciphering the complex interactions between DENV and host genes and pathways require accurate high-throughput measurements and comprehensive datasets and models. The purpose of this HIPC is to take advantage of recent advances in human immune profiling methods to characterize the early states of the human innate immune system following DENV infection and before and after vaccination against this infectious disease. The goal of the Genomics Core is to provide a central knowledge base and resource to define the human immune repertoire and develop predictors of disease and vaccine responses by using high throughput sequencing and bioinformatics that facilitate investigations of human immunity in well-characterized human cohorts. Other HIPC investigators will use this information to derive human immune profiles or signatures for disease in naturally acquired infection with known dengue immune status (Project 1), vaccine responsiveness and human challenge studies (Project 2), or DENV infection ex vivo with DENV strains of different virulence (Project 3). Network analysis of the human immune profiling data will identify pathways and genes for RNAi knockdown to determine how perturbations of the regulatory networks influence host responses during DENV infection. These studies are key to the overall goal of the HIPC to use high-throughput systems biology approaches to create molecular signatures that will define the human immune response profiles that correlate with the outcome of dengue virus infection or vaccination.