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.

多词核心（核心B） - 项目摘要 多派核心（核心B）将提供独特的，集中的散装，单细胞和空间分析功能 用于表型和功能性多词的分析，以告知BNAB的效率（项目） 1）和疫苗接种（项目2）针对HIV/SHIV/SIV病毒储备。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 - 小分析 （Panini，codex和Cosmx）具有独特的评估HIV病毒储层状态的既定能力。 与项目负责人和其他核心合作，Core B将利用其在批量，单一的批量专业知识 单元格和空间多媒体，以设计，概况和分析项目中的样本，提供必不可少的 技术支持以执行计划的研究。与计算分析核心C亲密接口 在下游，我们将授权深入的多模型理解，以帮助识别细胞和/或空间 可以预测或告知针对HIV病毒库的介入效率机制的签名。 核心的具体目的是：1）进行批量和单细胞基因组分析（RNA-Seq，atac-seq， 来自项目1和2的样品的PBMC和解离组织的Cite-Seq，病毒测序） 在存在下，精心策划的宿主免疫反应和病毒转录本的分子和细胞相关性 和没有干预； 2）使用定制的空间蛋白质组学和基因组学（RNA和DNA）使用 codex-panini在存在的情况下剖析病毒组织储量内的宿主 - 病原体相互作用 缺乏干预； 3）使用COSMX应用定制的目标空间转录组学识别 由于干预而在组织中精心策划的宿主免疫反应和病毒转录本的分子特征。 核心成员是单细胞和空间基因组技术开发领域的领导者，将 在每个阶段都参与所有项目。核心B将与其他研究人员进行样本准备， 手稿的处理，数据获取，质量控制和准备。核心C将由Drs共同主导。 Sizun Jiang（哈佛/BIDMC），Alex K. Shalek（MIT/Ragon/Broad）和Malika Boudries（BIDMC）。所有核心成员 在高质量散装，单细胞和空间多摩学数据生成的方法方面具有丰富的经验。 它们将与其他核心（例如计算核心C和NHP核心D）紧密合作 这项创新P01的各个方面的整合。具体而言，博士。 Shalek，Boudries和Jiang将监督批量 和单细胞相关的数据采集以及DRS。江和沙莱克将监督空间 - 摩尼斯数据获取 （codex-panini和cosmx）。总而言之，核心B将确保创新的技术平台以及 独特的评估HIV病毒储存剂态和细胞的能力可靠地应用于机械 在本P01中提出的研究是为了更深入地了解病毒储层及其目标性。