HGTDR: Advancing drug repurposing with heterogeneous graph transformers.

MOTIVATION: Drug repurposing is a viable solution for reducing the time and cost associated with drug development. However, thus far, the proposed drug repurposing approaches still need to meet expectations. Therefore, it is crucial to offer a systematic approach for drug repurposing to achieve cost savings and enhance human lives. In recent years, using biological network-based methods for drug repurposing has generated promising results. Nevertheless, these methods have limitations. Primarily, the scope of these methods is generally limited concerning the size and variety of data they can effectively handle. Another issue arises from the treatment of heterogeneous data, which needs to be addressed or converted into homogeneous data, leading to a loss of information. A significant drawback is that most of these approaches lack end-to-end functionality, necessitating manual implementation and expert knowledge in certain stages. RESULTS: We propose a new solution, Heterogeneous Graph Transformer for Drug Repurposing (HGTDR), to address the challenges associated with drug repurposing. HGTDR is a three-step approach for knowledge graph-based drug repurposing: (1) constructing a heterogeneous knowledge graph, (2) utilizing a heterogeneous graph transformer network, and (3) computing relationship scores using a fully connected network. By leveraging HGTDR, users gain the ability to manipulate input graphs, extract information from diverse entities, and obtain their desired output. In the evaluation step, we demonstrate that HGTDR performs comparably to previous methods. Furthermore, we review medical studies to validate our method's top 10 drug repurposing suggestions, which have exhibited promising results. We also demonstrated HGTDR's capability to predict other types of relations through numerical and experimental validation, such as drug-protein and disease-protein inter-relations. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/bcb-sut/HGTDR and http://git.dml.ir/BCB/HGTDR.

DeepDRA: Drug repurposing using multi-omics data integration with autoencoders.

Cancer treatment has become one of the biggest challenges in the world today. Different treatments are used against cancer; drug-based treatments have shown better results. On the other hand, designing new drugs for cancer is costly and time-consuming. Some computational methods, such as machine learning and deep learning, have been suggested to solve these challenges using drug repurposing. Despite the promise of classical machine-learning methods in repurposing cancer drugs and predicting responses, deep-learning methods performed better. This study aims to develop a deep-learning model that predicts cancer drug response based on multi-omics data, drug descriptors, and drug fingerprints and facilitates the repurposing of drugs based on those responses. To reduce multi-omics data's dimensionality, we use autoencoders. As a multi-task learning model, autoencoders are connected to MLPs. We extensively tested our model using three primary datasets: GDSC, CTRP, and CCLE to determine its efficacy. In multiple experiments, our model consistently outperforms existing state-of-the-art methods. Compared to state-of-the-art models, our model achieves an impressive AUPRC of 0.99. Furthermore, in a cross-dataset evaluation, where the model is trained on GDSC and tested on CCLE, it surpasses the performance of three previous works, achieving an AUPRC of 0.72. In conclusion, we presented a deep learning model that outperforms the current state-of-the-art regarding generalization. Using this model, we could assess drug responses and explore drug repurposing, leading to the discovery of novel cancer drugs. Our study highlights the potential for advanced deep learning to advance cancer therapeutic precision.