London Calling 2023: scNanoATAC-seq: a long-read single-cell assay to simultaneously detect chromatin accessibility and genetic variants

Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on the next-generation sequencing (NGS) platform is a powerful tool to decode chromatin states. However, it is difficult to detect structural variations (SVs) simultaneously with short-read sequencing. We developed scNanoATAC-seq, an scATAC-seq method based on a nanopore sequencing platform. The ability of scNanoATAC-seq to reveal chromatin accessibility features was comparable to that of the NGS-based scATAC-seq. Using scNanoATAC-seq, we discriminated parental alleles for each peak in GM12878 using genetic polymorphisms flanking the peak, which cannot be achieved by NGS-based scATAC-seq. Moreover, we simultaneously identified SVs and copy number variations using scNanoATAC-seq data.

Finally, we provided the direct evidence of co-accessibility between neighboring peaks from scNanoATAC-seq, where the chromatin accessibility of two sites in the same single cell was detected simultaneously by a long read. We will also discuss other third-generation sequencing platform-based single-cell epigenome
sequencing technologies.