Unsupervised cell functional annotation for single-cell RNA-seq

Genome Res. 2022 Jun 28;gr.276609.122. doi: 10.1101/gr.276609.122. Online ahead of print.


One of the first steps in the analysis of single-cell RNA sequencing data (scRNA-seq) is the assignment of cell types. While 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 datasets from several different organs. As we show, by using knowledge on gene sets, 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.