Motivation An essential part of drug discovery is the accurate prediction of the binding affinity of new compound-protein pairs. Most of the standard computational methods assume that compounds or proteins of the test data are observed during the training phase. However, in real-world situations, the test and training data are sampled from different domains with different distributions. To cope with this challenge, we propose a deep learning-based approach that consists of three steps. In the first step, the training encoder network learns a novel representation of compounds and proteins. To this end, we combine convolutional layers and LSTM layers so that the occurrence patterns of local substructures through a protein and a compound sequence are learned. Also, to encode the interaction strength of the protein and compound substructures, we propose a two-sided attention mechanism. In the second phase, to deal with the different distributions of the training and test domains, a feature encoder network is learned for the test domain by utilizing an adversarial domain adaptation approach. In the third phase, the learned test encoder network is applied to new compound-protein pairs to predict their binding affinity. Results To evaluate the proposed approach, we applied it to KIBA, Davis, and BindingDB datasets. The results show that the proposed method learns a more reliable model for the test domain in more challenging situations. Availability https://github.com/LBBSoft/DeepCDA
Drug-target Interactions (DTIs) prediction plays a central role in drug discovery. Computational methods in DTIs prediction have gotten more attention because carrying out in vitro and in vivo experiments on a large scale is costly and time-consuming. Machine learning methods, especially deep learning, are widely applied to DTIs prediction. In this study, the main goal is to provide a comprehensive overview of deep learning-based DTIs prediction approaches. Here, we investigate the existing approaches from multiple perspectives. We explore these approaches to find out which deep network architectures are utilized to extract features from drug compound and protein sequences. Also, the advantages and limitations of each architecture are analyzed and compared. Moreover, we explore the process of how to combine descriptors for drug and protein features. Likewise, a list of datasets that are commonly used in DTIs prediction is investigated. Finally, current challenges are discussed and a short future outlook of deep learning in DTI prediction is given.
The main problem of small molecule-based drug discovery is to find a candidate molecule with increased pharmacological activity, proper ADME, and low toxicity. Recently, machine learning has driven a significant contribution to drug discovery. However, many machine learning methods, such as deep learning-based approaches, require a large amount of training data to form accurate predictions for unseen data. In lead optimization step, the amount of available biological data on small molecule compounds is low, which makes it a challenging problem to apply machine learning methods. The main goal of this study is to design a new approach to handle these situations. To this end, source assay (auxiliary assay) knowledge is utilized to learn a better model to predict the property of new compounds in the target assay. Up to now, the current approaches did not consider that source and target assays are adapted to different target groups with different compounds distribution. In this paper, we propose a new architecture by utilizing graph convolutional network and adversarial domain adaptation network to tackle this issue. To evaluate the proposed approach, we applied it to Tox21, ToxCast, SIDER, HIV, and BACE collections. The results showed the effectiveness of the proposed approach in transferring the related knowledge from source to target data set.
Background Drug–target interaction (DTI) plays a vital role in drug discovery. Identifying drug–target interactions related to wet-lab experiments are costly, laborious, and time-consuming. Therefore, computational methods to predict drug–target interactions are an essential task in the drug discovery process. Meanwhile, computational methods can reduce search space by proposing potential drugs already validated on wet-lab experiments. Recently, deep learning-based methods in drug-target interaction prediction have gotten more attention. Traditionally, DTI prediction methods' performance heavily depends on additional information, such as protein sequence and molecular structure of the drug, as well as deep supervised learning. Results This paper proposes a method based on deep unsupervised learning for drug-target interaction prediction called AutoDTI++. The proposed method includes three steps. The first step is to pre-process the interaction matrix. Since the interaction matrix is sparse, we solved the sparsity of the interaction matrix with drug fingerprints. Then, in the second step, the AutoDTI approach is introduced. In the third step, we post-preprocess the output of the AutoDTI model. Conclusions Experimental results have shown that we were able to improve the prediction performance. To this end, the proposed method has been compared to other algorithms using the same reference datasets. The proposed method indicates that the experimental results of running five repetitions of tenfold cross-validation on golden standard datasets (Nuclear Receptors, GPCRs, Ion channels, and Enzymes) achieve good performance with high accuracy.
Motivation Screening bioactive compounds in cancer cell lines receive more attention. Multidisciplinary drugs or drug combinations have a more effective role in treatments and selectively inhibit the growth of cancer cells. Results Hence, we propose a new deep learning-based approach for drug combination synergy prediction called DeepTraSynergy. Our proposed approach utilizes multi-modal input including drug-target interaction, protein-protein interaction, and cell-target interaction to predict drug combination synergy. To learn the feature representation of drugs, we have utilized transformers. It is worth noting that our approach is a multi-task approach that predicts three outputs including the drug-target interaction, its toxic effect, and drug combination synergy. In our approach, drug combination synergy is the main task and the two other ones are the auxiliary tasks that help the approach to learn a better model. In the proposed approach three loss functions are defined: synergy loss, toxic loss, and drug-protein interaction loss. The last two loss functions are designed as auxiliary losses to help learn a better solution. DeepTraSynergy outperforms the classic and state-of-the-art models in predicting synergistic drug combinations on the two latest drug combination datasets. The DeepTraSynergy algorithm achieves accuracy values of 0.7715 and 0.8052 (an improvement over other approaches) on the DrugCombDB and Oncology-Screen datasets, respectively. Also, we evaluate the contribution of each component of DeepTraSynergy to show its effectiveness in the proposed method. The introduction of the relation between proteins (PPI networks) and drug-protein interaction significantly improves the prediction of synergistic drug combinations. Availability The source code and data are available at https://github.com/fatemeh-rafiei/DeepTraSynergy.
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