PathwayMind: An innovative tool and database for pathway perturbation analysis, uncovering critical pathways for drugs and target protein sets

Comput Biol Chem. 2025 Apr 15;118:108466. doi: 10.1016/j.compbiolchem.2025.108466. Online ahead of print.

ABSTRACT

Pathway enrichment analysis is a valuable tool for researchers aiming to understand the mechanisms underlying any specific drug or disease associated gene lists derived from biological assays or large-scale genome (omics) experiments. By employing this method, researchers can pinpoint biological pathways that exhibit a higher level of enrichment for a given set of genes than would be anticipated by random chance. These biological pathways play a crucial role in understanding the disease pathophysiology, therapeutic strategy, polypharmacological effects, synergistic mechanisms, and target engagement. However many of the available tools do not fulfill this requirement as most of the available tools consider a flat hierarchy of protein involvement in the pathway and do not consider topological information or importance of molecules in the pathway. Here we propose a novel method to enrich the molecular pathways and prioritize them based on their importance and crucial role in the biological function using the graph and evidence-based approach and customized datasets called PathwayMind. It includes 2648 pathways, 4539 biological events, 2465847 protein-protein interactions and 124717 gene-to-pathway relationships and the role of 3510 unique initial genes in 11,992 molecular pathways. The current manuscript comprises three major steps: The first step is about the data extraction and datasets creation for pathway enrichment, and the second steps comprises pathway perturbation analysis to identify most perturbed biological pathways and the third steps includes validation of this approach along with standalone tools and visualization algorithms which disclose the molecular involvement and improve the interpretability of the results. The end-to-end pathway analysis can be performed in a few minutes to provide complete insights of your target or drug of interest. The current PathwayMind tool and its datasets could be very useful for the molecular scientists and system biologists who are interested to understand the therapeutic effects of their drugs or understanding the involvement of biological pathways for specific gene sets which does not require any prior bioinformatics training.

PMID:40250332 | DOI:10.1016/j.compbiolchem.2025.108466