Single-cell ATAC-seq

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.title[
# Single-cell ATAC-seq
]
.author[
### Mikhail Dozmorov
]
.institute[
### Virginia Commonwealth University
]
.date[
### 2026-04-27
]

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## single-cell ATAC-seq agrees with bulk ATAC-seq

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<img src="img/scATAC-seq_overview.png" alt="" width="90%" style="display: block; margin: auto;" />
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.pull-right[ scATAC-seq (Single-cell Assay for Transposase-Accessible Chromatin using sequencing) - maps regions of the genome are "open" or "closed."

.small[ Chen, H., Lareau, C., Andreani, T. et al. Assessment of computational methods for the analysis of single-cell ATAC-seq data. Genome Biol 20, 241 (2019). https://doi.org/10.1186/s13059-019-1854-5 ]
]

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## scATAC-seq data

.small[Buenrostro, J., Wu, B., Litzenburger, U. et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486–490 (2015). https://doi.org/10.1038/nature14590]

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## single-cell ATAC-seq challenges

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* While for an expressed gene several RNA molecules are present in a single cell, scATAC-seq assays profile DNA, a molecule which is present in only two copies per cell (for a diploid organism).
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<img src="img/scATAC-seq_peaks_pct.png" alt="" width="400px" style="display: block; margin: auto;" />
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* The low copy number results in an inherent per-cell data sparsity, where only 1– 10% of expected accessible peaks are detected in single cells from scATAC-seq data, compared to 10–45% of expressed genes detected in single cells from scRNA-seq data.

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## single-cell ATAC-seq challenges

- The feature set in scATAC-seq includes genome-wide regions of accessible chromatin

- It is typically 10–20X the size of the feature set in scRNA-seq experiments (which is defined and limited by the number of genes expressed).

- A highly skewed distribution of accessibility across the genome, with a small number of peaks being detected in a large fraction of cells and a long tail of peaks being detected in only a few cells.