scNanoATAC-seq: a long-read single-cell ATAC sequencing method to detect chromatin accessibility and genetic variants simultaneously within an individual cell

The accessible chromatin regions were enriched in regulatory elements in human genome and many genetic variations associated with human diseases were identified within them. 1 Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on the next-generation sequencing (NGS) platform is a well-established method to detect open chromatin regions within an individual cell. 2 However, there remain challenges in detection of large-scale structural variations (SVs, including insertions, deletions, duplications, inversions and translocations) and haplotype phasing from scATAC-seq data, which can be well resolved by third-generation sequencing (TGS) platform-based single-molecule long-read sequencing. To integrate advantages of long-read sequencing into scATAC-seq, we developed single-cell assay for transposase‐accessible chromatin on Nanopore sequencing platform (scNanoATAC-seq), a plate-based scATAC-seq method suitable for TGS platform (Supplementary information, Fig. S1 ).