Analytical Approaches for ATAC-seq Data Analysis

ATAC-seq, the assay for transposase-accessible chromatin using sequencing, is a quick and efficient approach to investigating the chromatin accessibility landscape. Investigating chromatin accessibility has broad utility for answering many biological questions, such as mapping nucleosomes, identifying transcription factor binding sites, and measuring differential activity of DNA regulatory elements. Because the ATAC-seq protocol is both simple and relatively inexpensive, there has been a rapid increase in the availability of chromatin accessibility data. Furthermore, advances in ATAC-seq protocols are rapidly extending its breadth to additional experimental conditions, cell types, and species. Accompanying the increase in data, there has also been an explosion of new tools and analytical approaches for analyzing it. Here, we explain the fundamentals of ATAC-seq data processing, summarize common analysis approaches, and review computational tools to provide recommendations for different research questions. This primer provides a starting point and a reference for analysis of ATAC-seq data. © 2020 Wiley Periodicals LLC.