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bioRxiv · 10.1101/2020.10.14.340299

Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data

Zhang, J.·Liu, L.·Xu, T.·Zhang, W.·Zhao, C.·Li, S.·Li, J.·Rao, N.·Le, T. D.
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Abstract

BackgroundExisting computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level. However, as currently single-cell miRNA-mRNA co-sequencing data is just emerging and only available at small-scale, there is a strong need of novel methods to exploit existing single-cell data for the study of cell-specific miRNA regulation. ResultsIn this work, we propose a new method, CSmiR (Cell-Specific miRNA regulation) to use single-cell miRNA-mRNA co-sequencing data to identify miRNA regulatory networks at the resolution of individual cells. We apply CSmiR to the miRNA-mRNA co-sequencing data in 19 K562 single-cells to identify cell-specific miRNA-mRNA regulatory networks for understanding miRNA regulation in each K562 single-cell. By analyzing the obtained cell-specific miRNA-mRNA regulatory networks, we observe that the miRNA regulation in each K562 single-cell is unique. Moreover, we conduct detailed analysis on the cell-specific miRNA regulation associated with the miR-17/92 family as a case study. Finally, through exploring cell-cell similarity matrix characterized by cell-specific miRNA regulation, CSmiR provides a novel strategy for clustering single-cells to help understand cell-cell crosstalk. ConclusionsTo the best of our knowledge, CSmiR is the first method to explore miRNA regulation at a single-cell resolution level, and we believe that it can be a useful method to enhance the understanding of cell-specific miRNA regulation.

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Zhang, J., Liu, L., Xu, T., Zhang, W., Zhao, C., Li, S., Li, J., Rao, N., Le, T. D.. 2020-10-15. Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data. https://doi.org/10.1101/2020.10.14.340299

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