The measurement of both gene expression and DNA accessibility in the same cell creates an opportunity to link noncoding DNA elements to their potential regulatory targets through the correlation between DNA accessibility and the expression of a nearby gene12,17,20. We implemented a peak-to-gene linkage method in Signac based on recently described methods20. Briefly, we computed the Pearson correlation between the expression of a gene and the accessibility of each peak within 500 kb of the gene TSS and compared this value with the expected value given the GC content, overall accessibility and length of the peak (Methods). Applying this linkage method to all expressed genes in the PBMC dataset revealed a set of 37,424 peak–gene links with P < 0.05 across the genome (Fig. 2i). The majority (89%) of these links displayed a positive relationship between accessibility of the peak and expression of the linked gene. Although links were enriched in close proximity to the gene TSS, we also observed a substantial number of long-range putative regulatory relationships, with 58% of links spanning a distance of >100 kb from the
