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scKanFormer: A Transformer-KAN framework with biologically informed attention for cell type annotation in large-scale
Lin Yuan1,2, Junjie Cao1,2, Shengguo Sun1,2
1Key Laboratory of Computing Power Network and Information Security, Ministry of Education, Shandong Computer Science Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
Plos Computational Biology
|August 14, 2026
Summary
scKanFormer accurately annotates cell types in large single-cell RNA sequencing datasets. This Transformer-based framework overcomes batch effects and enhances biological interpretability for robust cell identification.
Area of Science:
- Genomics
- Computational Biology
- Bioinformatics
Background:
- Accurate cell type annotation is crucial for single-cell RNA sequencing (scRNA-seq) data analysis.
- Existing deep learning methods struggle with batch effects, interpretability, and handling large datasets.
Purpose of the Study:
- To develop a supervised framework, scKanFormer, for precise and robust cell type annotation in large-scale scRNA-seq data.
- To address limitations of interpretability and batch effect sensitivity in current annotation methods.
Main Methods:
- Utilized a Transformer architecture integrated with Kolmogorov-Arnold Networks (KAN) and Convolutional Neural Networks (CNN).
- Incorporated biological information, local, and global attention mechanisms.
- Avoided dimensionality reduction to maintain feature traceability.
Main Results:
- scKanFormer demonstrated precise, robust, and transferable high-resolution cell type annotations across benchmark datasets.
- The model showed insensitivity to batch effects and enhanced biological interpretability.
- Outperformed nine state-of-the-art methods in various cell type annotation scenarios.
Conclusions:
- scKanFormer offers a significant advancement in scRNA-seq data analysis, providing interpretable and batch-effect-resilient cell type annotations.
- The framework's design enhances the identification and interpretation of cellular features, paving the way for more reliable biological insights.

