Fundamental and practical approaches for single-cell ATAC-seq analysis

Assays for transposase-accessible chromatin through high-throughput sequencing (ATAC-seq) are effective tools in the study of genome-wide chromatin accessibility landscapes. With the rapid development of single-cell technology, open chromatin regions that play essential roles in epigenetic regulation have been measured at the single-cell level using single-cell ATAC-seq approaches. The application of scATAC-seq has become as popular as that of scRNA-seq. However, owing to the nature of scATAC-seq data, which are sparse and noisy, processing the data requires different methodologies and empirical experience. This review presents a practical guide for processing scATAC-seq data, from quality evaluation to downstream analysis, for various applications. In addition to the epigenomic profiling from scATAC-seq, we also discuss recent studies in which the function of non-coding variants has been investigated based on cell type-specific cis-regulatory elements and how to use the by-product genetic information obtained from scATAC-seq to infer single-cell copy number variants and trace cell lineage. We anticipate that this review will assist researchers in designing and implementing scATAC-seq assays to facilitate research in diverse fields.