Molecules, Vol. 28, Pages 1490: A Knowledge-Graph-Based Multimodal Deep Learning Framework for Identifying Drug–Drug Interactions

Molecules, Vol. 28, Pages 1490: A Knowledge-Graph-Based Multimodal Deep Learning Framework for Identifying Drug–Drug Interactions

Molecules doi: 10.3390/molecules28031490

Authors: Jing Zhang Meng Chen Jie Liu Dongdong Peng Zong Dai Xiaoyong Zou Zhanchao Li

The identification of drug–drug interactions (DDIs) plays a crucial role in various areas of drug development. In this study, a deep learning framework (KGCN_NFM) is presented to recognize DDIs using coupling knowledge graph convolutional networks (KGCNs) with neural factorization machines (NFMs). A KGCN is used to learn the embedding representation containing high-order structural information and semantic information in the knowledge graph (KG). The embedding and the Morgan molecular fingerprint of drugs are then used as input of NFMs to predict DDIs. The performance and effectiveness of the current method have been evaluated and confirmed based on the two real-world datasets with different sizes, and the results demonstrate that KGCN_NFM outperforms the state-of-the-art algorithms. Moreover, the identified interactions between topotecan and dantron by KGCN_NFM were validated through MTT assays, apoptosis experiments, cell cycle analysis, and molecular docking. Our study shows that the combination therapy of the two drugs exerts a synergistic anticancer effect, which provides an effective treatment strategy against lung carcinoma. These results reveal that KGCN_NFM is a valuable tool for integrating heterogeneous information to identify potential DDIs.