(635b) Single Cell Transcriptomic Atlases Deconvolve Cell-Free RNA Liquid Biopsies

Tissue of origin remains the at-best resolution of noninvasive liquid biopsy assays; however, incorporating knowledge from cellular pathophysiology, which often forms the basis of disease, would more closely match the resolution afforded by invasive procedures. Single cell transcriptomics are enabling dissection of the complex cellular heterogeneity and associated transcriptional programs underlying tissues. Here, we describe two approaches applying single cell transcriptomic data to resolve the cell types of origin of the cell free transcriptome. First, we used Tabula Sapiens, a whole-body transcriptomic cell atlas, to computationally deconvolve the cell-free transcriptome into a sum of cell type specific transcriptomes, to reveal the spectrum of cell types readily detectable in the blood. Second, we used individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset to create cell type signature scores which can be used to infer the implicated cell types from cell-free RNA liquid biopsy for a variety of diseases. Taken together, this work is one of the first direct clinical applications of single cell transcriptomic atlases to date. Our results demonstrate that cfRNA reflects cellular contributions in health and disease from diverse cell types, potentially enabling determination of pathophysiological changes of many cell types from a single blood test.