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

Mohammadzadeh-Vardin, T ; Sharif University of Technology | 2024

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  1. Type of Document: Article
  2. DOI: 10.1371/journal.pone.0307649
  3. Publisher: 2024
  4. Abstract:
  5. 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. Copyright: © 2024 Mohammadzadeh-Vardin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
  6. Keywords:
  7. Antineoplastic Agents ; Computational Biology ; Humans ; Neoplasms ; Ascorbic acid ; Blebbistatin ; Bleomycin ; Cytarabine ; Dabrafenib ; Dexamethasone ; Foretinib ; Gefitinib ; Gossypol ; Importazole ; Methylstat ; Momelotinib ; Neratinib ; Nilotinib ; Olaparib ; Schweinfurthin A ; Sotrastaurin ; Temsirolimus ; Tigecycline ; Tosedostat ; Unclassified drug ; Venetoclax ; Antineoplastic agent ; Accuracy ; Artificial intelligence ; Autoencoder ; Bioinformatics ; Controlled study ; Copy number variation ; Data integration ; Data mining ; Deep learning ; Drug industry ; Drug repositioning ; Drug response ; Epigenetics ; Female ; Gene expression ; Gene mutation ; Human ; Human cell ; Integration ; Learning algorithm ; Machine learning ; Major clinical study ; Omics ; Reliability ; Training ; Transcriptomics ; Drug therapy ; Multiomics ; Neoplasm ; Procedures
  8. Source: PLoS ONE ; Volume 19, Issue 7 JULY , 2024 ; 19326203 (ISSN)
  9. URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0307649