Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation

Abstract

As single-cell RNA sequencing technologies mature, massive gene expression profiles can be obtained. Consequently, cell clustering and annotation become two crucial and fundamental procedures affecting other specific downstream analyses. Most existing single-cell RNA-seq (scRNA-seq) data clustering algorithms do not take into account the available cell annotation results on the same tissues or organisms from other laboratories. Nonetheless, such data could assist and guide the clustering process on the target dataset. Identifying marker genes through differential expression analysis to manually annotate large amounts of cells also costs labor and resources. Therefore, in this paper, we propose a novel end-to-end cell supervised clustering and annotation framework called scAnCluster, which fully utilizes the cell type labels available from reference data to facilitate the cell clustering and annotation on the unlabeled target data. Our algorithm integrates deep supervised learning, self-supervised learning and unsupervised learning techniques together, and it outperforms other customized scRNA-seq supervised clustering methods in both simulation and real data. It is particularly worth noting that our method performs well on the challenging task of discovering novel cell types that are absent in the reference data.