A new and effective two-step clustering approach for single cell RNA sequencing data.

BACKGROUND: The rapid devolvement of single cell RNA sequencing (scRNA-seq) technology leads to huge amounts of scRNA-seq data, which greatly advance the research of many biomedical fields involving tissue heterogeneity, pathogenesis of disease and drug resistance etc. One major task in scRNA-seq data analysis is to cluster cells in terms of their expression characteristics. Up to now, a number of methods have been proposed to infer cell clusters, yet there is still much space to improve their performance. RESULTS: In this paper, we develop a new two-step clustering approach to effectively cluster scRNA-seq data, which is called TSC - the abbreviation of Two-Step Clustering. Particularly, by dividing all cells into two types: core cells (those possibly lying around the centers of clusters) and non-core cells (those locating in the boundary areas of clusters), we first clusters the core cells by hierarchical clustering (the first step) and then assigns the non-core cells to the corresponding nearest clusters (the second step). Extensive experiments on 12 real scRNA-seq datasets show that TSC outperforms the state of the art methods. CONCLUSION: TSC is an effective clustering method due to its two-steps clustering strategy, and it is a useful tool for scRNA-seq data analysis.