RT Journal Article
SR Electronic
T1 Destin: toolkit for single-cell analysis of chromatin accessibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 461905
DO 10.1101/461905
A1 Eugene Urrutia
A1 Li Chen
A1 Haibo Zhou
A1 Yuchao Jiang
YR 2019
UL http://biorxiv.org/content/early/2019/02/10/461905.abstract
AB Summary 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. Destin performs cell-type clustering via weighted principle component analysis, weighting accessible chromatin regions by existing genomic annotations and publicly available regulomic data sets. The weights and additional tuning parameters are determined via model-based likelihood. We evaluated the 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.Availability Destin toolkit is freely available as an R package at https://github.com/urrutiag/destin.Contact yuchaoj{at}email.unc.edu.