High-throughput combinatorial indexing enables scalable single-cell chromatin accessibility profiling [Validation]

While recent technical advancements have facilitated the mapping of epigenomes at the single-cell resolution, the throughput and quality of these methods have limited the widespread application of these technologies. Here, we describe a high-throughput platform for single-cell assay for transposase accessible chromatin (scATAC-seq) using droplet microfluidics that yields essential qualities for high-throughput profiling, including improvements in per-cell library complexity and throughput. This approach enables robust cell-typing of complex tissues and reveals a de novo atlas of cellular and epigenomic diversity across many cell types and cell stages. Overall design: A high-diversity library of random oligonucleotides were introduced to the dscATAC-seq assay, which was run uniformly with PBMCs at various bead input concentrations. To assess the bead merging algorithm (bap), we used overlap of oligonucleotide tags as an independent true positive means for barcodes pairs to then assess the precision and accuracy of our bead merging algorithm. The summary statistics for both bap1 and bap2 are shown here.