An accurate and robust imputation method scImpute for single-cell RNA-seq data

The emerging single-cell RNA sequencing (scRNA-seq) technologies enable the investigation of transcriptomic landscapes at the single-cell resolution. ScRNA-seq data analysis is complicated by excess zero counts, the so-called dropouts due to low amounts of mRNA sequenced within individual cells. We introduce scImpute, a statistical method to accurately and robustly impute the dropouts in scRNA-seq data. scImpute automatically identifies likely dropouts, and only perform imputation on these values without introducing new biases to the rest data. scImpute also detects outlier cells and excludes them from imputation. Evaluation based on both simulated and real human and mouse scRNA-seq data suggests that scImpute is an effective tool to recover transcriptome dynamics masked by dropouts. scImpute is shown to identify likely dropouts, enhance the clustering of cell subpopulations, improve the accuracy of differential expression analysis, and aid the study of gene expression dynamics.