SNuBar-ATAC – simple oligonucleotide-based multiplexing of single-cell chromatin accessibility

Microdroplet single-cell ATAC-seq is widely used to measure chromatin accessibility, however, highly scalable and simple sample multiplexing procedures are not available. UT MD Anderson Cancer Center researchers have developed a transposome-assisted single nucleus barcoding approach for ATAC-seq (SNuBar-ATAC) that utilizes a single oligonucleotide adaptor for multiplexing samples during the existing tagmentation step and does not require a pre-labeling procedure. The accuracy and scalability of SNuBar-ATAC was evaluated using cell line mixture experiments. The researchers applied SNuBar-ATAC to investigate treatment-induced chromatin accessibility dynamics by multiplexing 28 mice with lung tumors that received different combinations of chemo, radiation, and targeted immunotherapy. They also applied SNuBar-ATAC to study spatial epigenetic heterogeneity by multiplexing 32 regions from a human breast tissue. Additionally, they show that SNuBar can multiplex single cell ATAC and RNA multiomic assays in cell lines and human breast tissue samples. These data show that SNuBar is a highly accurate, easy-to-use, and scalable system for multiplexing scATAC-seq and scATAC and RNA co-assay experiments.

Availability – The code for the SNuBar method is available on the following GitHub repository:

Wang K, Xiao Z, Yan Y, Ye R, Hu M, Bai S, Sei E, Qiao Y, Chen H, Lim B, Lin SH, Navin NE. (2021) Simple oligonucleotide-based multiplexing of single-cell chromatin accessibility. Molecular Cell 81(20), 4319-4332.e10. [abstract]

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