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、集中的批量、单细胞和空间分析功能 对 bNAb 功效机制进行表型和功能多组学分析（项目 1) 和针对 HIV/SHIV/SIV 病毒库的疫苗接种（项目 2）。这些包括散装和单细胞 基因组方法（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 病毒库状态的独特能力。 与项目领导者和其他核心合作，核心 B 将利用其在批量、单一领域的深厚专业知识 细胞和空间多组学来设计、分析和分析项目中的样本，提供必要的 执行计划研究的技术支持。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，以帮助识别细胞和/或空间 可以预测或告知针对 HIV 病毒库的干预功效机制的特征。 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、 对来自项目 1 和 2 的样本进行 PBMC 和分离组织的 CITE-seq（病毒测序）以鉴定 精心策划的宿主免疫反应和存在的病毒转录物的分子和细胞相关性 以及缺乏干预； 2) 采用定制的空间蛋白质组学和基因组学（RNA 和 DNA） CODEX-PANINI 可在存在和存在的情况下在病毒组织库内原位剖析宿主与病原体的相互作用 缺乏干预； 3) 使用 CosMx 应用定制的靶向空间转录组学来识别 由于干预而精心策划的宿主免疫反应和组织中病毒转录的分子特征。 Core 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 参与每个阶段的所有项目。核心 B 将与其他研究人员进行样品准备工作， 处理、数据采集、质量控制和手稿准备。核心 C 将由博士共同领导。思尊 Jiang（哈佛大学/BIDMC）、Alex K. Shalek（麻省理工学院/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（例如计算核心 C 和 NHP 核心 D）紧密合作，以实现无缝 整合了这款创新 P01 的各个方面。具体来说，博士。 Shalek、Boudries 和 Jiang 将负责大宗业务 和单细胞相关数据采集，以及博士。 Jiang 和 Shalek 将监督空间组学数据采集 （CODEX-PANINI 和 CosMX）。总而言之，Core B将确保创新的技术平台， 评估 HIV 病毒库状态和细胞的独特能力已被强有力地应用于机制 本 P01 中提出的研究旨在更深入地了解病毒库及其靶向性。