Abstract 3691: Integrated multiomics unlocks holistic phenotypic insights allowing for deep molecular exploration

Abstract The omics era has greatly expanded the repertoire of approaches available for researchers and clinicians to unravel the complexity underpinning human health: Next Generation Sequencing (NGS) approaches can characterize genomes, epigenomes, transcriptomes, and proteomes. The analyses are critical to assess in individuals both pre- and post-treatment during therapeutic development and early-stage clinical trials. Peripheral blood mononuclear cells (PBMCs) offer a non-invasive approach that, when combined with omics tools, can provide a near holistic view of immune processes across patient cohorts. For fresh blood draws, this starts with automated sample handling and processing to ensure high viability and yield of PBMCs, along with simultaneous plasma separation and collection, which is then aliquoted for downstream analysis. These PBMC and plasma aliquots were then processed such that whole exome sequencing, whole genome methylation sequencing, single cell and bulk RNA sequencing, Olink Explore HT and Seer proteomic analysis, and metabolomic analysis can all be collected from patient blood draw. Integrated analysis across multiple data modalities allows for holistic views of pathways and processes that are highly impacted, with increased statistical significance than any one modality alone. Inclusion of dual proteomics assays provided a greater breadth of downstream functional results, revealing complementarity between assays. While genomics, transcriptomics, and proteomics provide information about genetic and functional potential, inclusion of metabolomics grants deeper phenotypic insights within and across individuals within a patient cohort. Ultimately, this approach reduces the need for repeated patient collections and lowers bio-storage requirements, making it a more patient-friendly and cost-effective solution, while rapidly producing a diverse set of multiomics results and allows for deep exploration of the molecular underpinnings of cancerous tissue. Citation Format: Andrea J. O'Hara, Tom Cohen, Ethan Stancliffe, Adam Richardson, David Corney, Laure Turner, Haythem Latif, Ginger Zhou. Integrated multiomics unlocks holistic phenotypic insights allowing for deep molecular exploration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3691.