Stacked ensemble-based mutagenicity prediction model using multiple modalities with graph attention network

Mutagenicity is a concern due to its association with genetic mutations which can result in a variety of negative consequences, including the development of cancer. Earlier identification of mutagenic compounds in the drug development process is therefore crucial for preventing the progression of unsafe candidates and reducing development costs. While computational techniques, especially machine learning models have become increasingly prevalent for this endpoint, they rely on a single modality. In this work, we introduce a novel stacked ensemble based mutagenicity prediction model which incorporate multiple modalities such as simplified molecular input line entry system (SMILES) and molecular graph. These modalities capture diverse information about molecules such as substructural, physicochemical, geometrical and topological. To derive substructural, geometrical and physicochemical information, we use SMILES, while topological information is extracted through a graph attention network (GAT) via molecular graph. Our model uses a stacked ensemble of machine learning classifiers to make predictions using these multiple features. We employ the explainable artificial intelligence (XAI) technique SHAP (Shapley Additive Explanations) to determine the significance of each classifier and the most relevant features in the prediction. We demonstrate that our method surpasses SOTA methods on two standard datasets across various metrics. Notably, we achieve an area under the curve of 95.21% on the Hansen benchmark dataset, affirming the efficacy of our method in predicting mutagenicity. We believe that this research will captivate the interest of both clinicians and computational biologists engaged in translational research.