Abstract
Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.
Highlights
Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin
Intestinal enterocyte disease (CKD)[25,26], hepatocytes in non-alcoholic steatohepatitis ple of why whole-body cell type characterization is relevant, we (NASH)/non-alcoholic fatty liver disease (NAFLD)[27] and mul- observed that a previous attempt to infer trophoblast cell types from tiple brain cell types in Alzheimer’s disease (AD)[28,29]
We found that several genes differentially expressed in NAFLD serum cfRNA7 were specific to the hepatocyte cell type profile derived above (P < 10−10, hypergeometric test)
Summary
Intestinal enterocyte disease (CKD)[25,26], hepatocytes in non-alcoholic steatohepatitis ple of why whole-body cell type characterization is relevant, we (NASH)/non-alcoholic fatty liver disease (NAFLD)[27] and mul- observed that a previous attempt to infer trophoblast cell types from tiple brain cell types in Alzheimer’s disease (AD)[28,29]. Using data from Ibarra et al, we discovered a striking decrease in the proximal tubule cell signature score of patients with CKD (ages 67–91 years, CKD stage 3–5 or peritoneal dialysis) compared to healthy controls (Fig. 2b and Extended Data Fig. 10a,b) These results demonstrate non-invasive resolution of proximal tubule deterioration observed in CKD histology[31] and are consistent with findings from invasive biopsy. We found that several genes differentially expressed in NAFLD serum cfRNA7 were specific to the hepatocyte cell type profile derived above (P < 10−10, hypergeometric test). We inferred neuronal death in plasma cfRNA between AD and healthy non-cognitive controls (NCIs) and observed differences in oligodendrocyte, oligodendrocyte progenitor and astrocyte signature scores (Fig. 2d and Extended Data Fig. 10). Online content Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/ s41587-021-01188-9
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