Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data

We develop Lisa (epigenetic Landscape In silico Sequence Analysis) to predict transcriptional regulators (TRs) of differentially expressed or co-expressed gene sets. Based on input gene sets, Lisa first uses histone mark ChIP-seq and chromatin accessibility profiles to construct a chromatin model related to the regulation of these genes. Using TR ChIP-seq peaks or imputed TR binding sites, Lisa probes the chromatin models using in silico deletion to find the most relevant TRs. Applied to gene sets derived from targeted TF perturbation experiments, Lisa boosts the performance of imputed TR cistromes, and outperforms alternative methods in identifying the perturbed TRs.