Unsupervised cell functional annotation for single-cell RNA-seq

One of the first steps in the analysis of single-cell RNA sequencing (scRNA-seq) data is the assignment of cell types. Although a number of supervised methods have been developed for this, in most cases such assignment is performed by first clustering cells in low-dimensional space and then assigning cell types to different clusters. To overcome noise and to improve cell type assignments, we developed UNIFAN, a neural network method that simultaneously clusters and annotates cells using known gene sets. UNIFAN combines both low-dimensional representation for all genes and cell-specific gene set activity scores to determine the clustering. We applied UNIFAN to human and mouse scRNA-seq data sets from several different organs. We show, by using knowledge about gene sets, that UNIFAN greatly outperforms prior methods developed for clustering scRNA-seq data. The gene sets assigned by UNIFAN to different clusters provide strong evidence for the cell type that is represented by this cluster, making annotations easier.