Fig. 2

Empirically parameterized simulation demonstrates Enhlink’s high accuracy. A Workflow to simulate promoter–enhancer associations parameterized by experimental data. The accessibilities of a promoter and its associated enhancers across cells are simulated from a single promoter–enhancer pair having a validated association. The simulated promoter accessibilities are derived by randomly shuffling the binary, scATAC-seq-derived accessibilities of the validated promoter across cells. Each simulated enhancer accessibility for a given cell is generated from the simulated promoter accessibility for that cell via a process that probabilistically flips the cell’s chromatin state: from closed to open (parameterized by λ _open) or from open to closed (λ _close). λ _open and λ _close are determined from the validated promoter–enhancer pair. The simulated enhancers are then integrated with the surrounding regions used as background. B λ _open and λ _close distribution parameters inferred from chromatin accessibility of enhancer–promoter pairs previously validated in human scATAC-seq cardiomyocyte cells (Hocker et. al 2021). Pairs involve the promoter KCNH2 or MYL2 as determined in all cells or in the subset of aCM or vCM cells. C f1-score (y axis) of simulated promoter–enhancer pairs as a function of average promoter accessibility and number of cells. Error bars summarize 20 simulated promoters. Each simulated promoter has between two and seven associated simulated enhancers