scRNMF: An imputation method for single-cell RNA-seq data by robust and non-negative matrix factorization

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool in genomics research, enabling the analysis of gene expression at the individual cell level. However, scRNA-seq data often suffer from a high rate of dropouts, where certain genes fail to be detected in specific cells due to technical limitations. This missing data can introduce biases and hinder downstream analysis. To overcome this challenge, the development of effective imputation methods has become crucial in the field of scRNA-seq data analysis. Here, we propose an imputation method based on robust and non-negative matrix factorization (scRNMF). Instead of other matrix factorization algorithms, scRNMF integrates two loss functions: L2 loss and C-loss. The L2 loss function is highly sensitive to outliers, which can introduce substantial errors. We utilize the C-loss function when dealing with zero values in the raw data. The primary advantage of the C-loss function is that it imposes a smaller punishment for larger errors, which results in more robust factorization when handling outliers. Various datasets of different sizes and zero rates are used to evaluate the performance of scRNMF against other state-of-the-art methods. Our method demonstrates its power and stability as a tool for imputation of scRNA-seq data.Author summary: It is still difficult to analyze scRNA-seq data because a significant portion of expressed genes have zeros. Gene expression levels can be restored through the imputation of scRNA-seq data, facilitating downstream analysis. To overcome this challenge, we propose an imputation method based on robust and non-negative matrix factorization (scRNMF). Instead of other matrix factorization algorithms, scRNMF integrates two loss functions: L2 loss and C-loss. Through the use of several simulated and real datasets, we perform an comprehensively evaluation of scRNMF against existing methods. scRNMF can enhance various aspects of downstream analysis, including gene expression data recovery, cell clustering analysis, gene differential expression analysis, and cellular trajectory reconstruction. The results of our study demonstrate that scRNMF is a powerful tool that can improve the accuracy of single-cell data analysis.