Single-cell RNA sequencing (scRNA-seq) technology has been widely applied to capture the heterogeneity of different cell types within complex tissues. An essential step in scRNA-seq data analysis is the annotation of cell types. Traditional cell-type annotation is mainly clustering the cells first, and then using the aggregated cluster-level expression profiles and the marker genes to label each cluster. Such methods are greatly dependent on the clustering results, which are insufficient for accurate annotation.


In this article, we propose a semi-supervised learning method for cell-type annotation called CALLR. It combines unsupervised learning represented by the graph Laplacian matrix constructed from all the cells and supervised learning using sparse logistic regression. By alternately updating the cell clusters and annotation labels, high annotation accuracy can be achieved. The model is formulated as an optimization problem, and a computationally efficient algorithm is developed to solve it. Experiments on 10 real datasets show that CALLR outperforms the compared (semi-)supervised learning methods, and the popular clustering methods.

Availability and implementation

The implementation of CALLR is available at

Supplementary information

Supplementary data are available at Bioinformatics online.

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