in the immediate promoter regions but may inevitably introduce a large number of false positives in the distal promoter/enhancer regions where the searching space becomes substantially larger. More and more studies showed that mutations within the distal regulatory elements, such as enhancer, insulator and silencer, could also disrupt or change the binding of TFs, nucleosome positioning signals and chromatin states. Furthermore, the locally changed chromosome conformation can block or create looping interaction between distal elements and promoter regions (14) and subsequently influence gene regulation. Unfortunately, few tools or resources have used such information to study genetic variants.
