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 aMulti-view 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 andSHADOW graph attention network, node feature learning based on 1DConvolutional neural network, and theAttention 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.

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.

Predicting the binding affinity of drug target is essential to reduce drug development costs and cycles. Recently, several deep learning-based methods have been proposed to utilize the structural or sequential information of drugs and targets to predict the drug-target binding affinity (DTA). However, methods that rely solely on sequence features do not consider hydrogen atom data, which may result in information loss. Graph-based methods may contain information that is not directly related to the prediction process. Additionally, the lack of structured division can limit the representation of characteristics. To address these issues, we propose a multimodal DTA prediction model using graph local substructures, called MLSDTA. This model comprehensively integrates the graph and sequence modal information from drugs and targets, achieving multimodal fusion through a cross-attention approach for multimodal features. Additionally, adaptive structure aware pooling is applied to generate graphs containing local substructural information. The model also utilizes the DropNode strategy to enhance the distinctions between different molecules. Experiments on two benchmark datasets have shown that MLSDTA outperforms current state-of-the-art models, demonstrating the feasibility of MLSDTA.

Exploring simple and efficient computational methods for drug repositioning has emerged as a popular and compelling topic in the realm of comprehensive drug development. The crux of this technology lies in identifying potential drug-disease associations, which can effectively mitigate the burdens caused by the exorbitant costs and lengthy periods of conventional drugs development. However, existing computational drug repositioning methods continue to encounter challenges in accurately predicting associations between drugs and diseases. In this paper, we propose a Multi-view Representation Learning method (MRLHGNN) with Heterogeneous Graph Neural Network for drug repositioning. This method is based on a collection of data from multiple biological entities associated with drugs or diseases. It consists of a view-specific feature aggregation module with meta-paths and auto multi-view fusion encoder. To better utilize local structural and semantic information from specific views in heterogeneous graph, MRLHGNN employs a feature aggregation model with variable-length meta-paths to expand the local receptive field. Additionally, it utilizes a transformer based semantic aggregation module to aggregate semantic features across different view-specific graphs. Finally, potential drug-disease associations are obtained through a multi-view fusion decoder with an attention mechanism. Cross-validation experiments demonstrate the effectiveness and interpretability of the MRLHGNN in comparison to nine state-of-the-art approaches. Case studies further reveal that MRLHGNN can serve as a powerful tool for drug repositioning.

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.

The rapid development of single-cell technology has opened up a whole new perspective for identifying cell types in multicellular organisms and understanding the relationships between them. Distinguishing different cell types and subtypes can identify the components of different immune cells and different tumor clones in the tumor microenvironment, which is the basic work of tumor heterogeneity analysis and can help researchers understand the mechanism of tumor immune escape. Existing algorithms treat both cell types and subtypes as populations of cells with specific gene expression patterns, which is not conducive to accurate cell typing. For that, we proposed a cell similarity metric that unifies cell type recognition and subtype identification (UCRSI), with the assumption that selectively expressed genes represent differences in underlying cell type with on/off manner, while differences in expression level represent different cell subtype with more/less manner. Our method calculates these two kinds of differences separately, and then combines them using a consensus adjacency matrix, and finally cell typing is completed using spectral clustering algorithm. The results show that UCRSI can reconstruct expert annotation of single-cell RNA sequencing datasets more robustly than existing methods. And, UCRSI is useful for analyzing tumor heterogeneity and improving visualization of large-scale cell clustering.

lncRNAs are involved in many biological processes, and their mutations and disorders are closely related to many diseases. Identification of LncRNA-Disease Associations (LDAs) helps us understand the pathogenesis of diseases and improve their diagnosis and treatment. However, experiments to determine LDAs are expensive, so it is essential to exploit effective computational methods to screen possible LDAs. In this study, we developed an LDA prediction model (LDA-DLPU) based on deep learning and positive-unlabeled (PU) learning. First, LDA-DLPU extracted features of lncRNAs and diseases based on singular value decomposition and regression model. Second, it selected negative LDAs based on PU learning and graph autoencoder. Finally, it classified unknown lncRNA-disease pairs based on deep neural network. LDA-DLPU obtained the best performance on two datasets. We predict that BCYRN1 and IFNG-AS1 may associate with leukemia.

Efficient mining of high-throughput data has become one of the popular themes in the big data era. Existing biology-related feature ranking methods mainly focus on statistical and annotation information. In this study, two efficient feature ranking methods are presented. Multi-target regression and graph embedding are incorporated in an optimization framework, and feature ranking is achieved by introducing structured sparsity norm. Unlike existing methods, the presented methods have two advantages: (1) the feature subset simultaneously account for global margin information as well as locality manifold information. Consequently, both global and locality information are considered. (2) Features are selected by batch rather than individually in the algorithm framework. Thus, the interactions between features are considered and the optimal feature subset can be guaranteed. In addition, this study presents a theoretical justification. Empirical experiments demonstrate the effectiveness and efficiency of the two algorithms in comparison with some state-of-the-art feature ranking methods through a set of real-world gene expression data sets.