The identification of drug-target interactions (DTIs) is an essential step in drug discovery. In vitro experimental methods are expensive, laborious, and time-consuming. Deep learning has witnessed promising progress in DTI prediction. However, how to precisely represent drug and protein features is a major challenge for DTI prediction. Here, we developed an end-to-end DTI identification framework called BINDTI based on bi-directional Intention network. First, drug features are encoded with graph convolutional networks based on its 2D molecular graph obtained by its SMILES string. Next, protein features are encoded based on its amino acid sequence through a mixed model called ACmix, which integrates self-attention mechanism and convolution. Third, drug and target features are fused through bi-directional Intention network, which combines Intention and multi-head attention. Finally, unknown drug-target (DT) pairs are classified through multilayer perceptron based on the fused DT features. The results demonstrate that BINDTI greatly outperformed four baseline methods (i.e., CPI-GNN, TransfomerCPI, MolTrans, and IIFDTI) on the BindingDB, BioSNAP, DrugBank, and Human datasets. More importantly, it was more appropriate to predict new DTIs than the four baseline methods on imbalanced datasets. Ablation experimental results elucidated that both bi-directional Intention and ACmix could greatly advance DTI prediction. The fused feature visualization and case studies manifested that the predicted results by BINDTI were basically consistent with the true ones. We anticipate that the proposed BINDTI framework can find new low-cost drug candidates, improve drugs’ virtual screening, and further facilitate drug repositioning as well as drug discovery. BINDTI is publicly available at https://github.com/plhhnu/BINDTI .

Background: Identifying possible drug-target interactions (DTIs) has become an important task in drug research and development. Although high-throughput screening is becoming available, experimental methods narrow down the validation space because of extremely high cost, low success rate, and time consumption. Therefore, various computational models have been exploited to infer DTI candidates. Methods: We introduced relevant databases and packages, mainly provided a comprehensive review of computational models for DTI identification, including network-based algorithms and machine learning-based methods. Specially, machine learning-based methods mainly include bipartite local model, matrix factorization, regularized least squares, and deep learning. Results: Although computational methods have obtained significant improvement in the process of DTI prediction, these models have their limitations. We discussed potential avenues for boosting DTI prediction accuracy as well as further directions.

Long noncoding RNAs (lncRNAs) participate in various biological processes and have close linkages with diseases. In vivo and in vitro experiments have validated many associations between lncRNAs and diseases. However, biological experiments are time-consuming and expensive. Here, we introduce LDA-VGHB, an lncRNA–disease association (LDA) identification framework, by incorporating feature extraction based on singular value decomposition and variational graph autoencoder and LDA classification based on heterogeneous Newton boosting machine. LDA-VGHB was compared with four classical LDA prediction methods (i.e. SDLDA, LDNFSGB, IPCARF and LDASR) and four popular boosting models (XGBoost, AdaBoost, CatBoost and LightGBM) under 5-fold cross-validations on lncRNAs, diseases, lncRNA–disease pairs and independent lncRNAs and independent diseases, respectively. It greatly outperformed the other methods with its prominent performance under four different cross-validations on the lncRNADisease and MNDR databases. We further investigated potential lncRNAs for lung cancer, breast cancer, colorectal cancer and kidney neoplasms and inferred the top 20 lncRNAs associated with them among all their unobserved lncRNAs. The results showed that most of the predicted top 20 lncRNAs have been verified by biomedical experiments provided by the Lnc2Cancer 3.0, lncRNADisease v2.0 and RNADisease databases as well as publications. We found that HAR1A, KCNQ1DN, ZFAT-AS1 and HAR1B could associate with lung cancer, breast cancer, colorectal cancer and kidney neoplasms, respectively. The results need further biological experimental validation. We foresee that LDA-VGHB was capable of identifying possible lncRNAs for complex diseases. LDA-VGHB is publicly available at https://github.com/plhhnu/LDA-VGHB.

Cell-to-cell communication (CCC) plays important roles in multicellular organisms. The identification of communication between cancer cells themselves and one between cancer cells and normal cells in tumor microenvironment helps understand cancer genesis, development and metastasis. CCC is usually mediated by Ligand-Receptor Interactions (LRIs). In this manuscript, we developed a Boosting-based LRI identification model (CellEnBoost) for CCC inference. First, potential LRIs are predicted by data collection, feature extraction, dimensional reduction, and classification based on an ensemble of Light gradient boosting machine and AdaBoost combining convolutional neural network. Next, the predicted LRIs and known LRIs are filtered. Third, the filtered LRIs are applied to CCC elucidation by combining CCC strength measurement and single-cell RNA sequencing data. Finally, CCC inference results are visualized using heatmap view, Circos plot view, and network view. The experimental results show that CellEnBoost obtained the best AUCs and AUPRs on the collected four LRI datasets. Case study in human head and neck squamous cell carcinoma (HNSCC) tissues demonstrates that fibroblasts were more likely to communicate with HNSCC cells, which is in accord with the results from iTALK. We anticipate that this work can contribute to the diagnosis and treatment of cancers.

COVID-19 has caused enormous challenges to global economy and public health. The identification of patients with the COVID-19 infection by CT scan images helps prevent its pandemic. Manual screening COVID-19-related CT images spends a lot of time and resources. Artificial intelligence techniques including deep learning can effectively aid doctors and medical workers to screen the COVID-19 patients. In this study, we developed an ensemble deep learning framework, DeepDSR, by combining DenseNet, Swin transformer, and RegNet for COVID-19 image identification. First, we integrate three available COVID-19-related CT image datasets to one larger dataset. Second, we pretrain weights of DenseNet, Swin Transformer, and RegNet on the ImageNet dataset based on transformer learning. Third, we continue to train DenseNet, Swin Transformer, and RegNet on the integrated larger image dataset. Finally, the classification results are obtained by integrating results from the above three models and the soft voting approach. The proposed DeepDSR model is compared to three state-of-the-art deep learning models (EfficientNetV2, ResNet, and Vision transformer) and three individual models (DenseNet, Swin transformer, and RegNet) for binary classification and three-classification problems. The results show that DeepDSR computes the best precision of 0.9833, recall of 0.9895, accuracy of 0.9894, F1-score of 0.9864, AUC of 0.9991 and AUPR of 0.9986 under binary classification problem, and significantly outperforms other methods. Furthermore, DeepDSR obtains the best precision of 0.9740, recall of 0.9653, accuracy of 0.9737, and F1-score of 0.9695 under three-classification problem, further suggesting its powerful image identification ability. We anticipate that the proposed DeepDSR framework contributes to the diagnosis of COVID-19.

Predicting potential drug-target interactions (DTIs) facilitates to accelerate drug discovery and reduce development cost. Current deep learning-based methods exhibit high-performance predictions, but three challenges remain: first, the absence of negative DTIs severely limits the model performance. Moreover, existing graph neural networks are beset with the scalability due to the model complexity and graph size. More importantly, most methods focus on learning the topological features while ignoring node features during DTI representation learning. To solve the limitations, here, we develop a multi-view neural network framework called DTI-MvSCA for DTI identification. This framework begins with constructing a drug-protein pair (DPP) network with matrix operation-based negative DTI selection, and then learns the DPP representations through a M ulti- v iew neural network, finally classifies each DPP based on multilayer perceptron. Particularly, the multi-view neural network integrates graph topological feature learning based on the self-attention mechanism and S HADOW graph attention network, node feature learning based on 1D C onvolutional neural network, and the A ttention mechanism. An in-depth experiment on DrugBank V3.0 and V5.0 showed that DTI-MvSCA obtained precise and robust predictions against five state-of-the-art baseline methods. Furthermore, visualizing the feature distributions of the selected negative DTIs exhibits a more distinguishable and clearer boundary. In summary, DTI-MvSCA provides a useful deep learning tool to investigate potential DTIs. It is freely available at https://github.com/plhhnu/DTI-MvSCA .