Discovering genetic biomarkers for targeted cancer therapeutics with eXplainable AI

Explainable Artificial Intelligence (XAI) enables a holistic understanding of the complex and nonlinear relationships between genes and prognostic outcomes of cancer patients. In this study, we focus on a distinct aspect of XAI – to generate accurate and biologically relevant hypotheses and provide a shorter and more creative path to advance medical research. We present an XAI-driven approach to discover otherwise unknown genetic biomarkers as potential therapeutic targets in high-grade serous ovarian cancer, evidenced by the discovery of IL27RA, which leads to reduced peritoneal metastases when knocked down in tumor-carrying mice given IL27-siRNA-DOPC nanoparticles. Summary Explainable Artificial Intelligence is amenable to generating biologically relevant testable hypotheses despite their limitations due to explanations originating from post hoc realizations.