Multi-Omics Core

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、单细胞和空间分析能力 对于影响bNAb疗效的表型和功能多组学分析(项目 1)和针对HIV/SHV/SIV病毒库的疫苗接种(项目2)。其中包括散装电池和单电池 基因组方法学(atac-seq、rna-seq、cite-seq和病毒测序)和空间基因组图谱 (Panini、Codex和CosMx)具有评估艾滋病毒病毒储存状态的独特能力。 通过与项目负责人和其他核心合作，Core B将利用其在批量、单一 细胞和空间多组学，以设计、分析和分析项目样本，提供必要的 为执行计划的研究提供技术支持。与计算分析核心C++的紧密接口 在下游，我们将增强对多模型的深入理解，以帮助识别细胞和/或空间 能够预测或告知针对艾滋病毒病毒库的干预效果的机制的签名。 核心的具体目标是：1)执行批量和单细胞基因组图谱(RNA-SEQ、ATAC-SEQ、 CITE-SEQ，病毒测序)项目1和2中的PBMC和分离组织的样本以识别 存在的协调宿主免疫反应和病毒转录本的分子和细胞相关性 和无干预；2)使用定制的空间蛋白质组学和基因组学(RNA和DNA) Codex-Panini在存在和存在的情况下原位剖析病毒组织储存库内宿主和病原体的相互作用 没有干预；以及，3)使用CosMx应用定制的靶向空间转录以识别 由于干预，组织中协调的宿主免疫反应和病毒转录本的分子特征。 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 在每个阶段参与所有项目。核心B将在样品准备过程中与其他调查人员对接， 处理、数据采集、质量控制和稿件准备。Core C将由Sizun博士共同领导 江(哈佛/BIDMC)、亚历克斯·K·沙莱克(麻省理工学院/拉贡/布罗德)和Malika Boudries(BIDMC)。所有核心成员 在高质量的批量、单细胞和空间多组学数据生成方法方面拥有丰富的经验。 他们将与其他核心(例如计算核心C和NHP核心D)密切合作，以实现无缝连接 融合了这一创新P01的方方面面。具体地说，沙莱克、布德里斯和江博士将监督散装 和单细胞相关的数据采集，江博士和沙莱克博士将负责空间组学数据采集 (CODEX-Panini和CosMX)。总而言之，核心B将确保创新的技术平台， 独一无二的评估艾滋病毒病毒储存状态和细胞的能力，被强有力地应用于 本P01中提出的研究，以更深入地了解病毒库及其靶向性。

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.