Cross-cellular analysis of chromatin accessibility markers H3K4me3 and DNase in the context of detecting cell-identity genes: An “all-or-nothing” approach

Cell identity is often associated to a subset of highly-expressed genes that define the cell processes, as opposed to essential genes that are always active. Cell-specific genes may be defined in opposition to essential genes, or via experimental means. Detection of said cell-specific genes is often a primary goal in the study of novel biosamples. Chromatin accessibility markers (such as DNase and H3K4me3) help identify actively transcribed genes, but data can be difficult to come by for entirely novel biosamples. In this study, we investigate the possibility of associating the cell-specificity status of genes with chromatin accessibility markers from different cell lines, and we suggest that the number of cell lines in which a gene is found to be marked by DNase/H3K4me3 is predictive of the essentiality status itself. We define a measure called the Cross-cellular Chromatin Openness (CCO) level, and show that it is associated with the essentiality status using two differentiation experiments. We then compare the CCO-level predictive power to existing scRNA-Seq and bulk RNA-Seq methods, showing it has good concordance when applicable.