Epi-Impute: Single-Cell RNA-seq Imputation via Integration with Single-Cell ATAC-seq

Single-cell RNA-seq data contains a lot of dropouts hampering downstream analyses due to the low number and inefficient capture of mRNAs in individual cells. Here, we present Epi-Impute, a computational method for dropout imputation by reconciling expression and epigenomic data. Epi-Impute leverages single-cell ATAC-seq data as an additional source of information about gene activity to reduce the number of dropouts. We demonstrate that Epi-Impute outperforms existing methods, especially for very sparse single-cell RNA-seq data sets, significantly reducing imputation error. At the same time, Epi-Impute accurately captures the primary distribution of gene expression across cells while preserving the gene-gene and cell-cell relationship in the data. Moreover, Epi-Impute allows for the discovery of functionally relevant cell clusters as a result of the increased resolution of scRNA-seq data due to imputation.