Multi-Omics Core

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.