Abstract 6611: Harnessing the power of multiomics from a single sample to explore tumor heterogeneity and advancing immuno-oncology research

Abstract The omics era has greatly expanded the repertoire of approaches available for researchers and clinicians to unravel the complexity behind cancer onset in humans: Next Generation Sequencing (NGS) approaches can characterize genomes, epigenomes, transcriptomes and proteomes of patient samples. Advanced DNA barcoding and automated microfluidics can take this to the next level, enabling multiomic characterization of single cells. Peripheral blood mononuclear cells (PBMCs) offer a window into the immune system that, when combined with these omics tools, can provide an insight into immune cells mediating anti-tumor responses in cancer patients. Here we detail a workflow using a single blood draw to rapidly produce a diverse set of multiomics results including genomics, epigenomics, transcriptomics and proteomics. This starts with automated sample handling and processing of the primary blood draw to ensure high viability and yield of PBMCs, along with simultaneous plasma separation and collection. These samples are then aliquoted and simultaneously processed for automated and semi-automated whole exome sequencing, single-cell RNA sequencing, methylation sequencing and Olink proteomics assay. Germline and somatic mutations can be detected using whole exome or whole genome sequencing with deep coverage, whereas methylation, ATAC or ChIP sequencing can be used for epigenetic characterization of the same sample. While bulk expression offers a high-level transcriptomics profile, single-cell transcriptomics facilitates detection of gene expression changes in each individual cell type, allowing for analysis of rare cell types including circulating tumor cells. Olink proteomic assays can be utilized for both biomarker discovery and validation, with highly targeted or broad-spectrum panels. With this robust workflow and advanced robotics for sample handling and processing to minimize potential batch effects, all these datatypes can be produced within days of primary sample collection using minimal sample amounts. High throughput integrative omics workflows, as described here, are useful in gaining a multidimensional view of cancer and advance immunotherapies by characterizing immune cell modulation in tumor progression, and can be expanded for use in tumor/normal analysis, evaluation of metastases and exploration of tumor microenvironment. Citation Format: Bhagyashree S. Birla, Andrea O'Hara, Elizabeth Louie, Ben Niu, Haythem Latif, Vanessa Tumilasci, Yang Han, Yongjun Fan, David Corney, Pranay Vishwanath, Wei Wang, Alfredo Staffa, Ilaria DeVito, Laure Turner, Chris Mozdzierz, Peter Nowacki, Ginger Zhou. Harnessing the power of multiomics from a single sample to explore tumor heterogeneity and advancing immuno-oncology research. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6611.