By including multiple replicates and doses per drug, we discover high-confidence drug-responsive chromatin regions and genes. We show that EZH2 degradation via MS177 coincides with up-regulation of NF-kB signaling, and SWI/SNF perturbation elicits a potent type I interferon response.

To combat this, we re-designed our MULTI-seq method and optimized it to enable pooled transposition of barcoded nuclei on the 10x Genomics scATAC-seq platform. We show that pooled transposition with MULTI-ATAC completely negates the batch effects that arise from processing samples separately.

For example, we see that variability in Tn5:nuclei ratios unsurprisingly skews per-nucleus fragment yields. However, this impacts dimensionality reduction and - importantly - even biases cell type recovery.