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Smart3-ATAC: a highly sensitive method for joint accessibility and full-length transcriptome analysis in single cells

Cheng, H.; Pui, H.-P.; Lentini, A.; Kolbeinsdottir, S.; Andrews, N.; Pei, Y.; Reinius, B.; Deng, Q.; Enge, M.

2021-12-03 systems biology
10.1101/2021.12.02.470912 bioRxiv
Show abstract

Joint single-cell measurements of gene expression and DNA regulatory element activity holds great promise as a tool to understand transcriptional regulation. Towards this goal we have developed Smart3-ATAC, a highly sensitive method which allows joint mRNA and chromatin accessibility analysis genome wide in single cells. With Smart3-ATAC, we are able to obtain the highest possible quality measurements per cell. The method combines transcriptomic profiling based on the highly sensitive Smart-seq3 protocol on cytosolic mRNA, with a novel low-loss single-cell ATAC (scATAC) protocol to measure chromatin accessibility. Compared to current droplet multiome methods, the yield of both the scATAC protocol and mRNA-seq protocol is markedly higher.

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