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CASB: a concanavalin A-based sample barcoding strategy for single-cell sequencing
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DOI：10.15252/msb.202010060.png)
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Sample multiplexing facilitates single-cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a concanavalin A-based sample barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase-accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications: 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-gamma-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-gamma response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability.
Keyword:
CASB
combinatorial sample indexing
sample multiplexing
single‐ cell RNA sequencing
single‐ nucleus ATAC sequencing
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