Accurate cell type annotation for single‐cell chromatin accessibility data via contrastive learning and reference guidance

Recent advances in single‐cell chromatin accessibility sequencing (scCAS) technologies have resulted in new insights into the characterization of epigenomic heterogeneity and have increased the need for automatic cell type annotation. However, existing automatic annotation methods for scCAS data fail to incorporate the reference data and neglect novel cell types, which only exist in a test set. Here, we propose RAINBOW, a reference‐guided automatic annotation method based on the contrastive learning framework, which is capable of effectively identifying novel cell types in a test set. By utilizing contrastive learning and incorporating reference data, RAINBOW can effectively characterize the heterogeneity of cell types, thereby facilitating more accurate annotation. With extensive experiments on multiple scCAS datasets, we show the advantages of RAINBOW over state‐of‐the‐art methods in known and novel cell type annotation. We also verify the effectiveness of incorporating reference data during the training process. In addition, we demonstrate the robustness of RAINBOW to data sparsity and number of cell types. Furthermore, RAINBOW provides superior performance in newly sequenced data and can reveal biological implication in downstream analyses. All the results demonstrate the superior performance of RAINBOW in cell type annotation for scCAS data. We anticipate that RAINBOW will offer essential guidance and great assistance in scCAS data analysis. The source codes are available at the GitHub website (BioX‐NKU/RAINBOW).