Imputation method for single-cell RNA-seq data using neural topic model

Single-cell RNA sequencing (scRNA-seq) technology studies transcriptome and cell-to-cell differences from higher single-cell resolution and different perspectives. Despite the advantage of high capture efficiency, downstream functional analysis of scRNA-seq data is made difficult by the excess of zero values (i.e., the dropout phenomenon). To effectively address this problem, we introduced scNTImpute, an imputation framework based on a neural topic model. A neural network encoder is used to extract underlying topic features of single-cell transcriptome data to infer high-quality cell similarity. At the same time, we determine which transcriptome data are affected by the dropout phenomenon according to the learning of the mixture model by the neural network. On the basis of stable cell similarity, the same gene information in other similar cells is borrowed to impute only the missing expression values. By evaluating the performance of real data, scNTImpute can accurately and efficiently identify the dropout values and imputes them accurately. In the meantime, the clustering of cell subsets is improved and the original biological information in cell clustering is solved, which is covered by technical noise. The source code for the scNTImpute module is available as open source at https://github.com/qiyueyang-7/scNTImpute.git.