SDImpute: A statistical block imputation method based on cell-level and gene-level information for dropouts in single-cell RNA-seq data

The single-cell RNA sequencing (scRNA-seq) technologies obtain gene expression at single-cell resolution and provide a tool for exploring cell heterogeneity and cell types. As the low amount of extracted mRNA copies per cell, scRNA-seq data exhibit a large number of dropouts, which hinders the downstream analysis of the scRNA-seq data. We propose a statistical method, SDImpute (Single-cell RNA-seq Dropout Imputation), to implement block imputation for dropout events in scRNA-seq data. SDImpute automatically identifies the dropout events based on the gene expression levels and the variations of gene expression across similar cells and similar genes, and it implements block imputation for dropouts by utilizing gene expression unaffected by dropouts from similar cells. In the experiments, the results of the simulated datasets and real datasets suggest that SDImpute is an effective tool to recover the data and preserve the heterogeneity of gene expression across cells. Compared with the state-of-the-art imputation methods, SDImpute improves the accuracy of the downstream analysis including clustering, visualization, and differential expression analysis.Author summary: Single-cell RNA sequencing (scRNA-seq) allows researchers to analyze gene expression of thousands of single cells simultaneously. However, the low amount of extracted mRNA leads to a large number of dropout events, which introduce computational challenges and hinder downstream analysis of data. To address this problem, we developed SDImpute, a novel statistical method to recover the scRNA-seq data based on cell-level and gene-level information in this manuscript. The goal of our algorithm is to denoise the scRNA-seq data while maintaining the biological nature of gene expression. Combining SDImpute with the downstream analysis tools, we considered the matched bulk expression data and known cell labels of the scRNA-seq data as criteria to design experiments to validate the performance of our method in both simulated and real datasets. Moreover, we offer an R package with detailed instructions and an example input dataset. We hope that SDImpute will be beneficial to researchers to identify mechanisms underlying some biological processes by analysis of the scRNA-seq data.