scWECTA: A weighted ensemble classification framework for cell type assignment based on single cell transcriptome.

Rapid advances in single-cell transcriptome analysis provide deeper insights into the study of tissue heterogeneity at the cellular level. Unsupervised clustering can identify potential cell populations in single-cell RNA-sequencing (scRNA-seq) data, but fail to further determine the identity of each cell. Existing automatic annotation methods using scRNA-seq data based on machine learning mainly use single feature set and single classifier. In view of this, we propose a Weighted Ensemble classification framework for Cell Type Annotation, named scWECTA, which improves the accuracy of cell type identification. scWECTA uses five informative gene sets and integrates five classifiers based on soft weighted ensemble framework. And the ensemble weights are inferred through the constrained non-negative least squares. Validated on multiple pairs of scRNA-seq datasets, scWECTA is able to accurately annotate scRNA-seq data across platforms and across tissues, especially for imbalanced data containing rare cell types. Moreover, scWECTA outperforms other comparable methods in balancing the prediction accuracy of common cell types and the unassigned rate of non-common cell types at the same time. The source code of scWECTA is freely available at https://github.com/ttren-sc/scWECTA.