 Abstract enhancers play a key role in gene regulation and can be used to understand how non-coding genetic variants affect complex traits. These enhancers are controlled by transcription factors and epigenetic mechanisms, but there is currently no framework for analyzing both together. Additionally, it is difficult to determine whether inferred gene regulatory networks are accurate or not due to the lack of a complete ground truth. To address this issue, researchers have developed two new tools called GRINIE and GRINPA. GRINIE uses chromatin accessibility data and RNA sequencing data from multiple samples to build enhanced mediated gene regulatory networks. GRINPA then evaluates the accuracy of these networks using a variety of metrics. The results show that these tools can accurately identify the TF pura as a regulator of pro-inflammatory macrophage polarization. This study demonstrates the importance of understanding gene regulatory networks involving enhancers and provides a framework for further investigation into the role of enhancers in disease. This article was authored by Arian Kamal, Christian Arnold, and Ike Claringbold, and others. We are article.tv, links in the description below.