Abstract
MOTIVATION: Recent advances in sequencing technology provide opportunities to study biological processes at a higher resolution. Cell type annotation is an important step in scRNA-seq analysis, which often relies on established marker genes. However, most of the previous methods divide the identification of cell types into two stages, clustering and assignment, whose performances are susceptible to the clustering algorithm, and the marker information cannot effectively guide the clustering process. Furthermore, their linear heuristic-based cell assignment process is often insufficient to capture potential dependencies between cells and types. RESULTS: Here, we present Interpretable Cell Type Annotation based on self-training (sICTA), a marker-based cell type annotation method that combines the self-training strategy with pseudo-labeling and the nonlinear association capturing capability of Transformer. In addition, we incorporate biological priori knowledge of genes and pathways into the classifier through an attention mechanism to enhance the transparency of the model. A benchmark analysis on 11 publicly available single-cell datasets demonstrates the superiority of sICTA compared to state-of-the-art methods. The robustness of our method is further validated by evaluating the prediction accuracy of the model on different cell types for each single-cell data. Moreover, ablation studies show that self-training and the ability to capture potential dependencies between cells and cell types, both of which are mutually reinforcing, work together to improve model performance. Finally, we apply sICTA to the pancreatic dataset, exemplifying the interpretable attention matrix captured by sICTA. AVAILABILITY AND IMPLEMENTATION: The source code of sICTA is available in public at https://github.com/nbnbhwyy/sICTA. The processed datasets can be found at https://drive.google.com/drive/folders/1jbqSxacL_IDIZ4uPjq220C9Kv024m9eL. The final version of the model will be permanently available at https://doi.org/10.5281/zenodo.13474010.