Core B - Genomics Core

核心 B - 基因组学核心

基本信息

批准号：
10153658
负责人：
Steven M Wolinsky
金额：
$ 30万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10153658
关键词：
Affect Antiviral Agents Binding Bioinformatics CD94 Antigen Cells ChIP-seq Clinical Communicable Diseases Complex Data Data Set Dengue Dengue Infection Dengue Virus Disease Flavivirus Gene Expression Genes Genetic Markers Genomics Genotype Goals High-Throughput Nucleotide Sequencing Human Human Genetics Immune Immune System Diseases Immune response Immunity Immunology Infection Information Resources Innate Immune System Investigation MHC Class I Genes Massive Parallel Sequencing Measurement Measures Messenger RNA Methods Modeling Molecular Profiling Outcome Pathogenesis Pathway Analysis Pathway interactions Pattern Pharmacotherapy Population Predisposition RNA RNA Interference Receptor Gene Research Personnel Resources Risk Serotyping Severity of illness Signal Pathway Structure Systems Biology Technology Testing Transcript Vaccination Vaccines Variant Vertebral column Virulence Virus Virus Diseases Yellow fever virus antiviral immunity base biomarker identification cell type cohort env Gene Products high throughput screening histone modification immunological status knock-down knowledge base mosquito-borne response single-cell RNA sequencing transcription factor transcriptome sequencing vaccination outcome vaccine response

项目摘要

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.

项目摘要对登革热病毒感染的先天免疫识别会引发抗病毒免疫反应；但是，有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）疾病发病机理和免疫力。旨在破译复合物的系统生物学方法 DENV和宿主基因与途径之间的相互作用需要准确的高通量测量值以及全面的数据集和模型。此HIPC的目的是利用最近的进步人类免疫分析方法以表征人类先天免疫系统的早期状态 DENV感染后以及针对这种传染病的疫苗接种之前和之后。目标的目标基因组学核心是提供中心知识基础和资源来定义人类免疫曲目并通过使用高吞吐量测序和在良好的人类人群中促进人类免疫力研究的生物信息学。其他 HIPC调查人员将使用此信息来得出人类的免疫特征或疾病特征自然获得的感染具有已知的登革率免疫状态（项目1），疫苗反应性和人类挑战研究（项目2）或DENV感染具有不同毒力的DENV菌株（项目3）。人类免疫分析数据的网络分析将确定RNAi敲低的途径和基因确定调节网络的扰动如何影响DENV感染期间的宿主反应。这些研究是HIPC使用高通量系统生物学方法的总体目标的关键创建将定义与人类免疫反应曲线的分子特征登革热病毒感染或疫苗接种的结果。