Tu210 - Deciphering Immune Cell Drivers of Health and Disease Through the Lens of a 40M Blood Cell Atlas

Abstract Text: Blood analysis is an essential clinical tool, providing an accessible window into human health. Broad shifts in major immune cell lineages in blood can be critical diagnostics; however, deeper profiling may uncover nuanced shifts in smaller subsets, revealing further clues to diagnosis, prognosis, disease manifestations and even treatment response. This level of granularity has the potential to redefine the clinical complete blood cell counts and identify cellular and biological programs that are shared and distinct across a range of immune disorders that could have therapeutic potential, setting the foundation towards developing precision medicine approaches for immune-mediated diseases. We employed single-cell multiomics technologies and generated an internal dataset across patients with checkpoint-inhibitor toxicity, infections, and autoimmune conditions. This internal dataset in combination with multiple external datasets, will culminate in a substantial dataset of ~10,000 donors and over 40M cells across 40 conditions. A dataset of this size will allow for mapping of all circulating cell subsets with a frequency of 0.001%. Downstream analysis of this unique dataset and immune cell subsets identified will explore differential abundance, transcriptional programs, localization of GWAS risk variants and immunoassays assessing cell functionality. Our preliminary analysis reassuringly recapitulates known biology, while also identifying novel immune cell subpopulations related to specific diseases. An Immune Cell Atlas of this size will not only define the wide spectrum of immune cell diversity across health and disease, but will undoubtedly be critical to expanding our knowledge of cross-disease immune cell programs, while simultaneously highlighting disease-specific variations.