scATAnno: Automated Cell Type Annotation for Single-cell ATAC-seq Data.

Recent advances in single-cell epigenomic techniques have increased the demand for single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) analysis. One key analytical task is to determine cell type identity based on epigenetic data. Here, we introduce scATAnno, a Python package designed to automatically annotate scATAC-seq data using large-scale scATAC-seq reference atlases. This workflow generates reference atlases from publicly available datasets, enabling accurate cell type annotation by integrating query data with reference atlases without the use of single-cell RNA sequencing (scRNA-seq) data. To enhance annotation accuracy, we incorporated k-nearest neighbors (KNN)-based and weighted distance-based uncertainty scores to effectively detect cell populations within the query data that are distinct from all cell types in the reference data. We compared and benchmarked scATAnno against five other published cell annotation approaches, demonstrating its superior performance across multiple datasets and metrics. We further showcased the utility of scATAnno across multiple datasets, including peripheral blood mononuclear cells (PBMCs), triple-negative breast cancer (TNBC), and basal cell carcinoma (BCC), and demonstrated that scATAnno accurately annotates cell types across diverse biological conditions. Overall, scATAnno is a useful tool for scATAC-seq reference atlas construction and cell type annotation and can facilitate the interpretation of new scATAC-seq datasets in complex biological systems. scATAnno is publicly available at https://scatanno-main.readthedocs.io/.