Drugst.One DREAM - Drug Repurposing through Expert Annotation and Modification

Complex diseases often lack an actionable understanding of their underlying causal biological mechanisms, which leads to treating symptoms rather than causes. Network and systems medicine define disease mechanisms through disease-associated genes, their encoded proteins, and their protein-protein interactions (PPIs), forming disease modules. With this, complex diseases can be subdivided into actionable causal mechanisms for potential precision and curative therapy by repurposing small-molecule drugs for new indications. However, current computational methods for disease module construction overlook pathway annotations, cellular compartments, and directed PPIs.As a consequence, disease modules require contextual refinement to identify dysregulations, select appropriate drug classes, and eliminate promiscuous proteins.Here, we present Drugst.One DREAM (Drug Repurposing through Expert Annotation and Modification), which equips biomedical experts with a user-friendly toolbox for disease module refinement that does not require bioinformatics expertise. This extension of the web tool Drugst.One introduces network editing features. Users can refine PPI modules supported by pathway enrichment analysis and network clustering. Dedicated graph layouts highlight sub-cellular localization and causal relationships queried from OmniPath. As an application case, we reproduce a previously described NOX5-containing module within this single web tool, showcasing its effectiveness in refining disease modules for a broad user group in pharmacology and biomedical research. In conclusion, the Drugst.One DREAM extension closes an important gap in the network medicine tool landscape by offering experts a user-friendly option for refining disease modules.