Graphical overview of the DegCre algorithm. (A) DegCre requires as inputs differential P-values for CRE signal and differential gene expression (pCRE and pDEG). DegCre also needs genomic distances between CREs and TSSs (d) as input. The lightning bolt indicates a perturbation has occurred to yield the lower depiction. (B) DegCre defines all possible associations between each CRE and TSS within a specified maximum distance. (C) DegCre bins associations by their distance (d) according to a heuristic that balances resolution versus maintaining the pCRE distribution (Methods). (D) DegCre calculates a raw association probability, araw,i,j, for a given pCRE,j by finding the fraction of expected true DEGs in the set of associations in the same distance bin and with a pCRE equal to or less than (more significant) pCRE,i. Plot shows actual data from ATAC-seq at 120 min from Reed et al. (2022). (E) DegCre corrects the raw association probability if the association does not involve a true DEG. (F) For CREs with multiple associations (nearly all CREs), associations across larger genomic distances are penalized by the probabilities that the CRE is associated to nearer DEGs. (G). The false-discovery rate (FDR) of the association is calculated based on a binomial distribution that uses the bin null association probability, abin, as the success probability. Created with BioRender (https://www.biorender.com).
