RegulomeXplorer: Interactive exploration of drug effects on subcellularly resolved proteomes

Mass spectrometry-based proteomics allows the quantification of drug-induced changes in protein abundance. However, the integration of perturbation data across subcellular compartments remains a challenging bottleneck. Here, we present RegulomeXplorer , a web-based tool for automated processing and interactive exploration of subcellular compartment-resolved proteomics data. RegulomeXplorer employs MaxQuant output files to determine differential protein regulations upon drug perturbation, performs functional enrichment analysis, and visualizes enriched terms on a two-dimensional cytoplasmic-nuclear plane, called regulome. The data visualization by means of regulomes allows to simultaneously assess the magnitude of drug perturbation effects within separate subcellular compartments as well as the contribution of regulated proteins to the position of each enriched term in the regulome plane. We validated RegulomeXplorer against previously published, manually curated regulome analyses. It was then applied on subcellular compartment resolved breast cancer cell line proteomes, revealing drug- and cell-line-specific responses to Doxorubicin and Taxol, both in line with their described mode of action. RegulomeXplorer provides an accessible workflow for interpreting compartment-resolved perturbation proteomics and generating mode of action hypotheses in drug-response studies. RegulomeXplorer is freely available without registration at https://chemnettools.anc.univie.ac.at/RegulomeExplorer/ .