A Graph Neural Network Model Enables Accurate Prediction of Anaplastic Lymphoma Kinase Inhibitors Compared to Other Machine Learning Models

Anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, is identified as a crucial target in the progression of anticancer therapeutics for non-small cell lung cancer. This study has executed a Graph Neural Network (GNN) model and compared it with three machine learning (ML) models based on fingerprints for rapid anticancer bioactivity prediction. ALK inhibitors with IC50 values were extracted from the REAXYS database. Following preprocessing, these inhibitors constituted a dataset of 1664 molecules. Subsequently, GNN and ML models were constructed on a training set. The generalizability of these models was assessed by internal and external validation procedures. The graph neural network model yielded promising results, with an average precision of $0.879\pm 0.041$ and an $F1$ score of $0.804\pm 0.049$ in cross-validation. In external validation, the model achieved an average precision of 0.938 and an $F1$ score of 0.863, surpassing the results of the ML models. Therefore, we can infer that the predictive model developed using the GNN is apt for the problem at hand and can be utilized to predict the biological activity of novel ALK inhibitors.