Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected predictions against several cancer types. To shed light on the decision-making process of CancerOmicsNet and to better understand the role of each kinase in the model, we employed a customized saliency map with adjustable channel weights. The saliency map, functioning as an explainable AI tool, allows for the analysis of input contributions to the output of a trained deep-learning model and facilitates the identification of essential kinases involved in tumor progression. The comprehensive survey of biomedical literature for essential kinases selected by CancerOmicsNet demonstrated that it could help pinpoint potential druggable targets for further investigation in diverse cancer types.
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Singha, Manali; Pu, Limeng; Srivastava, Gopal; Ni, Xialong; Stanfield, Brent A.; Uche, Ifeanyi K.; Rider, Paul J.F.; Kousoulas, Konstantin G.; Ramanujam, J.; and Brylinski, Michal, "Unlocking the Potential of Kinase Targets in Cancer: Insights from CancerOmicsNet, an AI-Driven Approach to Drug Response Prediction in Cancer" (2023). School of Medicine Faculty Publications. 1446.