Comberons from single cell transcriptomics in endothelial cells

Published on Jan 5, 2021in bioRxiv
· DOI :10.1101/2021.01.04.425317
S. Domanskyi (UCSD: University of California, San Diego), Sergii Domanskyi7
Estimated H-index: 7
(UCSD: University of California, San Diego)
+ 4 AuthorsN. Ferrara (UCSD: University of California, San Diego)
VEGF inhibitor drugs have been successful, especially in ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for a really effective therapy of angiogenesis-related diseases. In this paper we introduce a new concept, the comberon, a term named by analogy with the operon that refers to evolutionarily conserved combinations of co-expressed genes. These genes identify potential drug targets. Our results show that single-cell gene expression data can help to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and human) and enriched, within a network, of connections to up-regulated genes. This set does include VEGF receptors and includes several other receptors previously shown to play a role in angiogenesis. The conclusions are supported by multiple highly significant statistical tests from large datasets, including an independent validation set. This discovery has broad pharmacological and socio-economic implications, going beyond angiogenesis therapy.
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