Pathway-based analysis holds promise to be instrumental in precision and personalized medicine analytics. However, the majority of pathway-based analysis methods utilize “fixed” or “rigid” data sets that limit their ability to account for complex biological inter-dependencies. Here, we present REDESIGN: RDF-based Differential Signaling Pathway informatics framework. The distinctive feature of the REDESIGN is that it is designed to run on “flexible” ontology-enabled data sets of curated signal transduction pathway maps to uncover high explanatory differential pathway mechanisms on gene-to-gene level. The experiments on two morphoproteomic cases demonstrated REDESIGN’s capability to generate actionable hypotheses in precision/personalized medicine analytics.