ScCAEs: deep clustering of single-cell RNA-seq via convolutional autoencoder embedding and soft K-means.

Clustering and cell type classification are a vital step of analyzing scRNA-seq data to reveal the complexity of the tissue (e.g. the number of cell types and the transcription characteristics of the respective cell type). Recently, deep learning-based single-cell clustering algorithms become popular since they integrate the dimensionality reduction with clustering. But these methods still have unstable clustering effects for the scRNA-seq datasets with high dropouts or noise. In this study, a novel single-cell RNA-seq deep embedding clustering via convolutional autoencoder embedding and soft K-means (scCAEs) is proposed by simultaneously learning the feature representation and clustering. It integrates the deep learning with convolutional autoencoder to characterize scRNA-seq data and proposes a regularized soft K-means algorithm to cluster cell populations in a learned latent space. Next, a novel constraint is introduced to the clustering objective function to iteratively optimize the clustering results, and more importantly, it is theoretically proved that this objective function optimization ensures the convergence. Moreover, it adds the reconstruction loss to the objective function combining the dimensionality reduction with clustering to find a more suitable embedding space for clustering. The proposed method is validated on a variety of datasets, in which the number of clusters in the mentioned datasets ranges from 4 to 46, and the number of cells ranges from 90 to 30 302. The experimental results show that scCAEs is superior to other state-of-the-art methods on the mentioned datasets, and it also keeps the satisfying compatibility and robustness. In addition, for single-cell datasets with the batch effects, scCAEs can ensure the cell separation while removing batch effects.

ScLRTC: imputation for single-cell RNA-seq data via low-rank tensor completion.

BACKGROUND: With single-cell RNA sequencing (scRNA-seq) methods, gene expression patterns at the single-cell resolution can be revealed. But as impacted by current technical defects, dropout events in scRNA-seq lead to missing data and noise in the gene-cell expression matrix and adversely affect downstream analyses. Accordingly, the true gene expression level should be recovered before the downstream analysis is carried out. RESULTS: In this paper, a novel low-rank tensor completion-based method, termed as scLRTC, is proposed to impute the dropout entries of a given scRNA-seq expression. It initially exploits the similarity of single cells to build a third-order low-rank tensor and employs the tensor decomposition to denoise the data. Subsequently, it reconstructs the cell expression by adopting the low-rank tensor completion algorithm, which can restore the gene-to-gene and cell-to-cell correlations. ScLRTC is compared with other state-of-the-art methods on simulated datasets and real scRNA-seq datasets with different data sizes. Specific to simulated datasets, scLRTC outperforms other methods in imputing the dropouts closest to the original expression values, which is assessed by both the sum of squared error (SSE) and Pearson correlation coefficient (PCC). In terms of real datasets, scLRTC achieves the most accurate cell classification results in spite of the choice of different clustering methods (e.g., SC3 or t-SNE followed by K-means), which is evaluated by using adjusted rand index (ARI) and normalized mutual information (NMI). Lastly, scLRTC is demonstrated to be also effective in cell visualization and in inferring cell lineage trajectories. CONCLUSIONS: a novel low-rank tensor completion-based method scLRTC gave imputation results better than the state-of-the-art tools. Source code of scLRTC can be accessed at https://github.com/jianghuaijie/scLRTC .