Adverse Drug Reaction Discovery Using a Tumor-Biomarker Knowledge Graph.

Adverse drug reactions (ADRs) are a major public health concern, and early detection is crucial for drug development and patient safety. Together with the increasing availability of large-scale literature data, machine learning has the potential to predict unknown ADRs from current knowledge. By the machine learning methods, we constructed a Tumor-Biomarker Knowledge Graph (TBKG) which contains four types of node: Tumor, Biomarker, Drug, and ADR using biomedical literatures. Based on this knowledge graph, we not only discovered potential ADRs of antitumor drugs but also provided explanations. Experiments on real-world data show that our model can achieve 0.81 accuracy of three cross-validation and the ADRs discovery of Osimertinib was chosen for the clinical validation. Calculated ADRs of Osimertinib by our model consisted of the known ADRs which were in line with the official manual and some unreported rare ADRs in clinical cases. Results also showed that our model outperformed traditional co-occurrence methods. Moreover, each calculated ADRs were attached with the corresponding paths of "tumor-biomarker-drug" in the knowledge graph which could help to obtain in-depth insights into the underlying mechanisms. In conclusion, the tumor-biomarker knowledge-graph based approach is an explainable method for potential ADRs discovery based on biomarkers and might be valuable to the community working on the emerging field of biomedical literature mining and provide impetus for the mechanism research of ADRs.