ATAC-Seq is an assay for interrogating the entire genome for accessibility to DNA binding proteins in a single experiment. In collaboration with Jay Shendure’s lab and scientists at Illumina, we recently developed sci-ATAC-seq, a single-cell ATAC-seq protocol. Our initial study, led by Darren Cusanovich, explored variation in chromatin accessibility both between and within populations of single cells. Our single-cell ATAC-Seq relies on combinatorial cellular indexing, and thus does not require the physical isolation of individual cells during library construction. The technique scales sublinearly in time and cost and can profile thousands of individual cells in a single experiment.

Analyzing single-cell ATAC-Seq experiments is challenging because the datasets tend to be large, sparse, and binary. Conventional single-cell analysis approaches such as principal component analysis are not well suited to this sort of data. We are working on new techniques to glean insights about cell state and gene regulation from single-cell ATAC-Seq experiments.

Papers

High-Capacity sample multiplexing for single cell chromatin accessibility profiling

The continuum of Drosophila embryonic development at single-cell resolution

Single-cell analysis of chromatin and expression reveals age- and sex-associated alterations in the human heart

Joint profiling of chromatin accessibility and gene expression in thousands of single cells

Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data

A single-cell atlas of in vivo mammalian chromatin accessibility

The cis-regulatory dynamics of embryonic development at single-cell resolution

Defining cell types and states with single-cell genomics

Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing