scATAnno: Automated Cell Type Annotation for single-cell ATAC Sequencing Data.

The recent advances in single-cell epigenomic techniques have created a growing demand for scATAC-seq analysis. One key task is to determine cell types based on epigenetic profiling. We introduce scATAnno, a workflow designed to automatically annotate scATAC-seq data using large-scale scATAC-seq reference atlases. This workflow can generate scATAC-seq reference atlases from publicly available datasets, and enable accurate cell type annotation by integrating query data with reference atlases, without the aid of scRNA-seq profiling. To enhance annotation accuracy, we have incorporated KNN-based and weighted distance-based uncertainty scores to effectively detect unknown cell populations within the query data. We showcase the utility of scATAnno across multiple datasets, including peripheral blood mononuclear cell (PBMC), basal cell carcinoma (BCC) and Triple Negative Breast Cancer (TNBC), and demonstrate that scATAnno accurately annotates cell types across conditions. Overall, scATAnno is a powerful tool for cell type annotation in scATAC-seq data and can aid in the interpretation of new scATAC-seq datasets in complex biological systems.