Destin: toolkit for single-cell analysis of chromatin accessibility

Single-cell assay of transposase-accessible chromatin followed by sequencing (scATAC-seq) is an emerging new technology for the study of gene regulation with single-cell resolution. The data from scATAC-seq are unique - sparse, binary, and highly variable even within the same cell type. As such, neither methods developed for bulk ATAC-seq nor single-cell RNA-seq data are appropriate. Here, we present Destin, a bioinformatic and statistical framework for comprehensive scATAC-seq data analysis. We evaluated performance of Destin using downsampled bulk ATAC-seq data of purified samples and scATAC-seq data from seven diverse experiments. Compared to existing methods, Destin was shown to outperform across all data sets and platforms. For demonstration, we further applied Destin to 2,088 adult mouse forebrain cells and identified cell type-specific association of previously reported schizophrenia GWAS loci.