EnTSSR: A Weighted Ensemble Learning Method to Impute Single-Cell RNA Sequencing Data

The advancements of single-cell RNA sequencing (scRNA-seq) technologies have provided us unprecedented opportunities to characterize cellular states and investigate the mechanisms of complex diseases. Due to technical issues such as dropout events, scRNA-seq data contains excess of false zero counts, which has a substantial impact on the downstream analyses. Although several computational approaches have been proposed to impute dropout events in scRNA-seq data, there is no strong consensus on which is the best approach. In this study, we propose a novel weighted ensemble learning method, named EnTSSR, to impute dropout events in scRNA-seq data. By using a multi-view two-side sparse self-representation framework, our model can exploit the consensus similarities between genes and between cells based on the imputed results of various imputation methods. Moreover, we introduce a weighted ensemble strategy to leverage the information captured by various imputation methods effectively. Down-sampling experiments, clustering analysis, differential expression analysis and cell trajectory inference are carried out to evaluate the performance of our proposed model. Experiment results demonstrate that our EnTSSR can effectively recover the true expression pattern of scRNA-seq data.