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A key challenge to ensure its real-life adoption lies in translating the outcomes of complex AI-driven data integration and modeling into a form easily understood by the clinical audience. To ensure explainability, knowledge graphs have emerged as data models integrating multi-omics data sources and representing them as interconnected networks. Knowledge graphs offer a framework which AI models can progressively refine, highlighting the most influential features and relationships facilitating transparency of complex interactions and interdependencies. In this perspective we present major components and challenges upon developing a knowledge-based explainable AI system. 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