Multi-Omics Core

多组学核心

• 批准号: 10724221
• 负责人: Sizun Jiang
• 金额: $ 24.78万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-11 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724221
• 关键词: ATAC-seq; Affect; Antibodies; Biological; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Chromatin; Clinical; Collaborations; Computer Analysis; DNA; Data; Dissociation; Ensure; Environment; Generations; Genomics; Goals; HIV; Human Resources; Imaging technology; Immune response; Immunologics; Immunotherapeutic agent; In Situ; Infection; Intervention; Investigation; Manuscripts; Measures; Methodology; Methods; Modeling; Molecular; Molecular Profiling; Multiomic Data; Peripheral Blood Mononuclear Cell; Phenotype; Population; Preparation; Proteins; Proteomics; Quality Control; RNA; Research Personnel; SIV; Sampling; Signal Pathway; Surface Antigens; Testing; Tissue Sample; Tissues; Transcript; Treatment Efficacy; Vaccination; Vaccine Therapy; Viral; Viral reservoir; Work; data acquisition; data sharing; design; empowerment; experience; experimental study; innovation; innovative technologies; member; multiple omics; neutralizing antibody; pathogen; response; simian human immunodeficiency virus; single cell analysis; single cell sequencing; success; technology development; technology platform; transcriptome sequencing; transcriptomics; tumor-immune system interactions

Multi-omics Core (Core B) – Project Summary The Multi-omics Core (Core B) will provide unique, centralized bulk, single-cell, and spatial profiling capabilities for phenotypic and functional multi-omics analyses of the mechanisms informing the efficacy of bNAb (Project 1) and vaccination (Project 2) against the HIV/SHIV/SIV viral reservior. These include bulk and single-cell genomic methodologies (ATAC-seq, RNA-seq, CITE-seq and viral sequencing), and spatial-omic profiling (PANINI, CODEX and CosMx) with the unique established ability to assess HIV viral reservoir states. In collaboration with Project Leaders and other Cores, Core B will leverage its deep expertise in bulk, single- cell, and spatial multi-omics to design, profile, and analyze samples from the Projects, providing essential technical support to execute the planned studies. Interfacing intimately with the Computational Analysis Core C downstream, we will empower a deep, multi-model understanding to help identify cellular and/or spatial signatures that can predict or inform mechanisms of interventional efficacy against HIV viral reservoirs. The Specific Aims of the Core are to: 1) Perform bulk and single-cell genomic profiling (RNA-seq, ATAC-seq, CITE-seq, viral sequencing) of PBMC and dissociated tissues for samples from Projects 1 & 2 to identify molecular and cellular correlates of orchestrated host immune responses and viral transcripts in the presence and absence of intervention; 2) Employ customized Spatial Proteomics and Genomics (RNA and DNA) using CODEX-PANINI to dissect host-pathogen interactions in situ within viral tissue reservoirs in the presence and absence of intervention; and, 3) Apply customized targeted Spatial Transcriptomics with CosMx to identify molecular signatures of orchestrated host immune responses and viral transcripts in tissues due to intervention. Core B members are leaders in the fields of single-cell and spatial genomic technology development, and will be involved in all Projects at every stage. Core B will interface with the other investigators in sample preparation, processing, data acquisition, quality control, and preparation of manuscripts. Core C will be co-led by Drs. Sizun Jiang (Harvard/BIDMC), Alex K. Shalek (MIT/Ragon/Broad), and Malika Boudries (BIDMC). All Core members have extensive experience in methods for high quality bulk, single-cell and spatial multi-omics data generation. They will work closely with the other cores (e.g., Computational Core C and NHP Core D) for seamless integration of all aspects of this innovative P01. Specifically, Drs. Shalek, Boudries and Jiang will oversee bulk and single-cell related data acquisition, and Drs. Jiang and Shalek will oversee spatial-omics data acqusition (CODEX-PANINI and CosMX). In summary, Core B will ensure that innovative technological platforms, with the unique established ability to assess HIV viral reservoir states and cells, are robustly applied to the mechanistic studies proposed in this P01, to yield a deeper understanding of the viral reservoir and its targetability.

多组学核心（核心B）-项目摘要 多组学核心（核心B）将提供独特的集中式批量、单细胞和空间分析功能 用于对bNAb疗效机制进行表型和功能多组学分析（项目 1)和针对HIV/SHIV/SIV病毒储库的疫苗接种（项目2）。其中包括散装和单细胞 基因组学方法（ATAC-seq、RNA-seq、CITE-seq和病毒测序）和空间组学分析 （PANINI，CODEX和CosMx），具有评估HIV病毒储存库状态的独特能力。 通过与项目负责人和其他核心的合作，核心B将利用其在批量、单个 细胞和空间多组学来设计，分析和分析项目中的样品，提供必要的 提供技术支持以执行计划的研究。与计算分析核心C紧密连接 在下游，我们将赋予深入的多模型理解能力，以帮助识别细胞和/或空间 这些特征可以预测或告知针对HIV病毒储库的干预功效的机制。 核心的具体目标是：1）进行批量和单细胞基因组分析（RNA-seq，ATAC-seq， CITE-seq，病毒测序），以鉴定来自项目1和2的样品的PBMC和解离组织的DNA序列。 在存在病毒的情况下，协调的宿主免疫应答和病毒转录物的分子和细胞相关性 2）采用定制的空间蛋白质组学和基因组学（RNA和DNA）， CODEX-PANINI在存在和不存在病毒的情况下， 没有干预;和，3）应用定制的靶向空间转录组学与CosMx，以确定 协调的宿主免疫应答的分子特征和由于干预而在组织中的病毒转录物。 核心B成员是单细胞和空间基因组技术开发领域的领导者，并将 参与项目的每个阶段。核心B将在样本制备中与其他研究者进行沟通， 数据处理、数据采集、质量控制和手稿准备。核心C将由Sizun博士共同领导 Jiang（哈佛/BIDMC），Alex K. Shalek（MIT/Ragon/Broad）和Malika Boudries（BIDMC）。所有核心成员 在高质量批量、单细胞和空间多组学数据生成方法方面拥有丰富的经验。 它们将与其他核心密切合作（例如，计算核心C和NHP核心D）， 这一创新P01的各个方面的整合。具体来说，Shalek博士，Boudries博士和Jiang博士将监督散装 和单细胞相关的数据采集，姜博士和Shalek将监督空间组学数据采集 （CODEX-PANINI和CosMX）。总之，核心B将确保创新的技术平台， 独特的建立能力，以评估艾滋病毒的水库状态和细胞，是强大的适用于机制， 本P01中提出的研究，以更深入地了解病毒库及其靶向性。