LiMeNEx: an interactive webserver on lipid biochemical gene-regulatory network

Lipid metabolism represents an intricate landscape of biochemical reactions catalyzed by enzymes and regulated by transcription factors (TFs) to maintain metabolic homeostasis. Disruption of the enzymatic or transcriptional machinery is associated with lipid imbalance, contributing to diverse pathological conditions across tissues and the physiological system. However, existing pathway resources predominantly focus on metabolic map reactions but lack integration of upstream regulatory components, limiting system-level interrogation of lipid-associated mechanisms. We present LiMeNEx (Lipid Metabolic Network Explorer), an interactive webserver for exploration of lipid biochemical gene regulatory networks that link lipids, enzymes, and TFs. LiMeNEx integrates carefully curated 504 biochemical reactions across 22 lipid pathways, involving 330 enzymatic genes and 345 TFs mapped across 50 human tissues and 11 physiological systems. The three consols of LiMeNEx allow users to query lipids for visualization of lipid pathways and genes involved in lipid-enzyme reactions, and to explore tissue and systems-specific transcriptional regulators of target genes. LiMeNEx provides a holistic view of lipid metabolism with comprehensive documentation for intuitive navigation. By integrating metabolic and regulatory layers in a tissue-resolved framework, it enables hypothesis-driven system-level investigation of lipid metabolism and related disorders. LiMeNEx is freely available at https://limenex.raylab.iiitd.edu.in/.