WEDGE: imputation of gene expression values from single-cell RNA-seq datasets using biased matrix decomposition

Hu, Yinlei; Li, Bin; Zhang, Wen; Liu, Nianping; Cai, Pengfei; Chen, Falai; Qu, Kun

The low capture rate of expressed RNAs from single-cell sequencing technology is one of the major obstacles to downstream functional genomics analyses. Recently, a number of imputation methods have emerged for single-cell transcriptome data, however, recovering missing values in very sparse expression matrices remains a substantial challenge. Here, we propose a new algorithm, WEDGE (WEighted Decomposition of Gene Expression), to impute gene expression matrices by using a biased low-rank matrix decomposition method (bLRMD). WEDGE successfully recovered expression matrices, reproduced the cell-wise and gene-wise correlations, and improved the clustering of cells, performing impressively for applications with multiple cell type datasets with high dropout rates. Overall, this study demonstrates a potent approach for imputing sparse expression matrix data, and our WEDGE algorithm should help many researchers to more profitably explore the biological meanings embedded in their scRNA-seq datasets.