Importantly, chromVAR provides robust results for 10,000 fragments per cell, a typical number of fragments generated from a single-cell using scATAC-seq4 (Supplementary Figure 7). By projecting the vector of bias corrected deviations from individual cells into two dimensions using tSNE11, chromVAR enables the reconstruction of the major hematopoietic lineages using 10,000 fragments per sample. With this analytical framework, we can also visualize the TFs associated with significant chromatin accessibility within each simulated single cell epigenome, thereby correctly identifying known master regulators of hematopoiesis, including HOXA9, SPI1, TBX21, and GATA112–15 (Fig. 1c).