Spatial transcriptomics (ST) helps us understand cell interactions, developmental processes, and disease progression within tissues by analyzing gene expression while preserving spatial information on tissue sections. However, the spatial distribution patterns of the same cell population may differ in different slice samples, and a single slice is difficult to adapt to spatial changes, making multi-slice integration methods a research hotspot in recent years. Traditional graph convolution relies on a fixed graph structure, whose adjacency relationships remain fixed during training. It cannot be adaptively updated according to feature changes and is difficult to reflect the spatial distribution differences between different slices. Dynamic graph convolutional neural networks (DGCNN), on the other hand, adaptively update based on node embeddings or features during training to capture complex spatial relationships. Therefore, we propose DGAE, a framework based on DGCNN for multi-slice ST data alignment and data enhancement. DGAE consists of two modules: DGAE_align and DGAE_recog. DGAE_align combines K-nearest neighbor (KNN) and r-radius to build a hybrid graph, and integrates the spatial information of different slices to achieve accurate spatial alignment. DGAE_recog aggregates the information of adjacent slices into the target slice for data enhancement, achieving effective transmission of information between different slices. Experimental results show that DGAE outperforms existing methods in multi-slice ST data alignment and also demonstrates superior performance in data enhancement tasks. In addition, DGAE has shown well adaptability and stability in spatial domain recognition, denoising and disease research, demonstrating the wide applicability and scalability of DGAE as a method for multi-slice ST data alignment and data enhancement.

Compared with monotherapy, combination drug therapy plays a crucial role in clinical treatment. However, the exponential expansion of the drug combination space has rendered traditional exploration methods for synergistic drug combinations inadequate. Recently, numerous efficient and accurate computational approaches have been developed to predict anticancer drug synergy, particularly those leveraging hypergraphs to model the multifaceted relationships between drug combinations and cell lines, which have demonstrated remarkable potential. Nevertheless, existing hypergraph-based methods fail to account for the heterogeneity of anticancer synergy hypergraphs and overlook the underlying similarities among drugs and cell lines, thereby limiting their ability to fully capture the complex interactions between drug combinations and cell lines. To address these limitations, we propose an Adaptive Heterogeneous Hypergraph Representation Learning Method (HHGSynergy) for predicting anticancer drug synergy, enabling more precise identification of synergistic drug combinations. Specifically, our framework first constructs drug/cell line similarity-based synergy hypergraphs based on the foundational anticancer synergy hypergraph, thereby establishing a comprehensive heterogeneous hypergraph. Next, a node importance calculation module is employed to learn both local and global importance weights of nodes, effectively capturing the structural characteristics of the hypergraph. Finally, a type-specific multi-head attention mechanism is utilized to iteratively update node embeddings, adaptively learning the significance of heterogeneous hyperedges. Experimental results demonstrate that HHGSynergy achieves state-of-the-art performance in both classification and regression tasks across diverse experimental scenarios, outperforming existing leading models. Case studies further underscore its potential for discovering novel synergistic drug combinations.

Circular RNA (circRNA) is a widely distributed class of non-coding RNA molecules that have been shown to play a significant role in cancer development and drug resistance, significantly influencing cellular sensitivity to therapeutic drugs and treatment outcomes. However, traditional biomedical experimental methods are limited by low efficiency and high costs when verifying the association between circular RNA and drug sensitivity. Therefore, developing an efficient and accurate computational method to predict new associations between circRNA and drug sensitivity has become an urgent need in current research. To address this, this study proposes HECLCDA, a novel method based on heterogeneous cross-scale contrastive learning. To construct a comprehensive initial information base for drugs and circRNAs, circRNA gene sequence similarity, drug structural inclusion similarity (SIS), and Gaussian kernel similarity were integrated.Based on the integrated and complete known information of circRNAs and drugs, a heterogeneous graph was built. The model used the Heterogeneous Graph Transformer to extract heterogeneous network topological information, effectively distinguishing the heterogeneity of nodes and edges. The model broke through the information relationship between node attributes and network topology at two scales, and innovatively introduced a cross-scale contrastive learning mechanism in a sparse labeling scenario. Using self-supervised signals, we aimed to enhance the discriminative power of node embeddings and maximize the mutual information between paired nodes at different scales. Cross-validation experiments demonstrated that HECLCDA performs excellently on real data and can efficiently predict drug sensitivity. Additionally, case studies further validate the model's effectiveness in predicting potential circRNA-drug sensitivity associations.

Based on the analysis of user behavior on microvideo platforms, we find that the more times users have explicit interactions with the videos posted by vloggers, the higher the possibility of explicit interactions between users and vloggers. However, the existing recommendation models mainly rely on the direct interests between users and items to model user preferences, and fail to explore the potential interests between users and items from multiple perspectives, resulting in incomplete modeling of user preferences. In response to the above problems, this paper proposes a multi-view augmented graph neural network model for micro-video vlogger recommendation (MAGNN). Specifically, we simultaneously construct bipartite graphs of the user-vlogger interaction relationship and the uservideo interaction relationship to fully capture the direct and potential vlogger preferences of users from different views. Furthermore, we have designed a bi-directional cross-attention with cross-dot-product fusion module. It adaptively learns the correlation between the preference features of different views through the dual paths of forward propagation and backward propagation, and optimizes the attention mechanism by using the cross-dot-product mechanism to enhance the discriminative ability of the attention mechanism. We conducted a large number of experiments on two public datasets. The experimental results fully verify the effectiveness of the method we propose in the recommendation task of micro-video vloggers.

Survival prediction serves as a pivotal component in precision oncology, enabling the optimization of treatment strategies through mortality risk assessment. While the integration of histopathological images and genomic profiles offers enhanced potential for patient stratification, existing methodologies are constrained by two fundamental limitations: (i) insufficient attention to fine-grained local features in favor of global representations, and (ii) suboptimal cross-modal fusion strategies that either neglect intrinsic correlations or discard modality-specific information. To address these challenges, we propose DSCASurv, a novel cross-modal fusion alignment framework designed to explore and integrate intrinsic correlations across multimodal data, thereby improving the accuracy of survival prediction. Specifically, DSCASurv leverages the local feature extraction capabilities of convolutional layers and the long-range dependency modeling of scanning state space models to extract intra-modal representations, while generating cross-modal representations through dual parallel mixer architectures. A cross-modal attention module functions as a bridge for inter-modal information exchange and complementary information transfer. The framework ultimately integrates all intra-modal representations to generate survival predictions by enhancing and recalibrating complementary information. Extensive experiments on five benchmark cancer datasets demonstrate the superior performance of our approach compared to existing methods.

Advancements in spatial transcriptomics (ST) technology have enabled the analysis of gene expression while preserving cellular spatial information, greatly enhancing our understanding of cellular interactions within tissues. Accurate identification of spatial domains is crucial for comprehending tissue organization. However, the effective integration of spatial location and gene expression still faces significant challenges. To address this challenge, we propose a novel self-supervised graph representation learning framework named stHGC for identifying spatial domains. Firstly, a hybrid neighbor graph is constructed by integrating different similarity metrics to represent spatial proximity and high-dimensional gene expression features. Secondly, a self-supervised graph representation learning framework is introduced to learn the representation of spots in ST data. Within this framework, the graph attention mechanism is utilized to characterize relationships between adjacent spots, and the self-supervised method ensures distinct representations for non-neighboring spots. Lastly, a spatial regularization constraint is employed to enable the model to retain the structural information of spatial neighbors. Experimental results demonstrate that stHGC outperforms state-of-the-art methods in identifying spatial domains across ST datasets with different resolutions. Furthermore, stHGC has been proven to be beneficial for downstream tasks such as denoising and trajectory inference, showcasing its scalability in handling ST data.

Circular RNA (circRNA) is a class of noncoding RNA that is highly conserved and exhibit exceptional stability. Due to its function as a microRNA sponge, circRNA has gained significant attention as an essential biomarker and potential drug target in the pathogenesis of several cancers. Although many circRNAs have been identified to play a role in cancer resistance, traditional methods are time-consuming and expensive. In this context, computational methods offer a promising way to facilitate the discovery process. However, most existing prediction models focus on the association between circRNAs and drug resistance, without considering the corresponding disease-related information in the circRNA-drug resistance association. Incorporating disease-related information into the prediction of circRNA-drug resistance associations could potentially improve the efficiency and speed of discovering and developing circRNA-targeting drugs. We propose a computational framework, named GraphCDD, for predicting the association between circRNA and drug resistance. Our model utilizes data from three sources, namely circRNA, disease, and drug, to construct three similarity networks that represent the features of circRNA, disease, and drug, respectively. We utilize a multimodal graph neural network to acquire efficient representations of circRNAs, diseases, and drugs by integrating various types of information, and establish a predictive model. The experimental results have validated the effectiveness of our model and provided a promising method in predicting potential associations between circRNA and drug resistance.

Predicting potential drug-disease associations (RDAs) plays a pivotal role in elucidating therapeutic strategies for diseases and facilitating drug repositioning, making it of paramount importance. However, existing methods are constrained and rely heavily on limited domain-specific knowledge, impeding their ability to effectively predict candidate associations between drugs and diseases. Moreover, the simplistic definition of unknown information pertaining to drug-disease relationships as negative samples presents inherent limitations. To overcome these challenges, we introduce a novel hierarchical negative sampling-based graph contrastive model, termed HSGCLRDA, which aims to forecast latent associations between drugs and diseases. In this study, HSGCLRDA integrates the association information as well as similarity between drugs, diseases and proteins. Meanwhile, the model constructs a drug-disease-protein heterogeneous network. Subsequently, employing a hierarchical structural sampling technique, we establish reliable negative drug-disease samples utilizing PageRank algorithms. Utilizing meta-path aggregation within the heterogeneous network, we derive low-dimensional representations for drugs and diseases, thereby constructing global and local feature graphs that capture their interactions comprehensively. To obtain representation information, we adopt a self-supervised graph contrastive approach that leverages graph convolutional networks (GCNs) and second-order GCNs to extract feature graph information. Furthermore, we integrate a contrastive cost function derived from the cross-entropy cost function, facilitating holistic model optimization. Experimental results obtained from benchmark datasets not only showcase the superior performance of HSGCLRDA compared to various baseline methods in predicting RDAs but also emphasize its practical utility in identifying novel potential diseases associated with existing drugs through meticulous case studies.

Studies have shown that IncRNA-miRNA interactions can affect cellular expression at the level of gene molecules through a variety of regulatory mechanisms and have important effects on the biological activities of living organisms. Several biomolecular network-based approaches have been proposed to accelerate the identification of lncRNA-miRNA interactions. However, most of the methods cannot fully utilize the structural and topological information of the lncRNA-miRNA interaction network. In this article, we proposed a new method, ISLMI, a prediction model based on information injection and second order graph convolution network(SOGCN). The model calculated the sequence similarity and Gaussian interaction profile kernel similarity between lncRNA and miRNA, fused them to enhance the intrinsic interaction between the nodes, using SOGCN to learn second-order representations of similarity matrix information. At the same time, multiple feature representations obtain using different graph embedding methods were also injected into the second-order graph representation. Finally, matrix complementation was used to increase the model accuracy. The model combined the advantages of different methods and achieved reliable performance in 5-fold cross-validation, significantly improved the performance of predicting lncRNA-miRNA interactions. In addition, our model successfully confirmed the superiority of ISLMI by comparing it with several other model algorithm.

MOTIVATION: CircularRNA (circRNA) is a class of noncoding RNA with high conservation and stability, which is considered as an important disease biomarker and drug target. Accumulating pieces of evidence have indicated that circRNA plays a crucial role in the pathogenesis and progression of many complex diseases. As the biological experiments are time-consuming and labor-intensive, developing an accurate computational prediction method has become indispensable to identify disease-related circRNAs. RESULTS: We presented a hybrid graph representation learning framework, named GraphCDA, for predicting the potential circRNA-disease associations. Firstly, the circRNA-circRNA similarity network and disease-disease similarity network were constructed to characterize the relationships of circRNAs and diseases, respectively. Secondly, a hybrid graph embedding model combining Graph Convolutional Networks and Graph Attention Networks was introduced to learn the feature representations of circRNAs and diseases simultaneously. Finally, the learned representations were concatenated and employed to build the prediction model for identifying the circRNA-disease associations. A series of experimental results demonstrated that GraphCDA outperformed other state-of-the-art methods on several public databases. Moreover, GraphCDA could achieve good performance when only using a small number of known circRNA-disease associations as the training set. Besides, case studies conducted on several human diseases further confirmed the prediction capability of GraphCDA for predicting potential disease-related circRNAs. In conclusion, extensive experimental results indicated that GraphCDA could serve as a reliable tool for exploring the regulatory role of circRNAs in complex diseases.

MOTIVATION: Accumulating evidences have indicated that microRNA (miRNA) plays a crucial role in the pathogenesis and progression of various complex diseases. Inferring disease-associated miRNAs is significant to explore the etiology, diagnosis and treatment of human diseases. As the biological experiments are time-consuming and labor-intensive, developing effective computational methods has become indispensable to identify associations between miRNAs and diseases. RESULTS: We present an Ensemble learning framework with Resampling method for MiRNA-Disease Association (ERMDA) prediction to discover potential disease-related miRNAs. Firstly, the resampling strategy is proposed for building multiple different balanced training subsets to address the challenge of sample imbalance within the database. Then, ERMDA extracts miRNA and disease feature representations by integrating miRNA-miRNA similarities, disease-disease similarities and experimentally verified miRNA-disease association information. Next, the feature selection approach is applied to reduce the redundant information and increase the diversity among these subsets. Lastly, ERMDA constructs an individual learner on each subset to yield primitive outcomes, and the soft voting method is introduced for making the final decision based on the prediction results of individual learners. A series of experimental results demonstrates that ERMDA outperforms other state-of-the-art methods on both balanced and unbalanced testing sets. Besides, case studies conducted on the three human diseases further confirm the ERMDA's prediction capability for identifying potential disease-related miRNAs. In conclusion, these experimental results demonstrate that our method can serve as an effective and reliable tool for researchers to explore the regulatory role of miRNAs in complex diseases.

MOTIVATION: Discovering the drug-target interactions (DTIs) is a crucial step in drug development such as the identification of drug side effects and drug repositioning. Since identifying DTIs by web-biological experiments is time-consuming and costly, many computational-based approaches have been proposed and have become an efficient manner to infer the potential interactions. Although extensive effort is invested to solve this task, the prediction accuracy still needs to be improved. More especially, heterogeneous network-based approaches do not fully consider the complex structure and rich semantic information in these heterogeneous networks. Therefore, it is still a challenge to predict DTIs efficiently. RESULTS: In this study, we develop a novel method via Multiview heterogeneous information network embedding with Hierarchical Attention mechanisms to discover potential Drug-Target Interactions (MHADTI). Firstly, MHADTI constructs different similarity networks for drugs and targets by utilizing their multisource information. Combined with the known DTI network, three drug-target heterogeneous information networks (HINs) with different views are established. Secondly, MHADTI learns embeddings of drugs and targets from multiview HINs with hierarchical attention mechanisms, which include the node-level, semantic-level and graph-level attentions. Lastly, MHADTI employs the multilayer perceptron to predict DTIs with the learned deep feature representations. The hierarchical attention mechanisms could fully consider the importance of nodes, meta-paths and graphs in learning the feature representations of drugs and targets, which makes their embeddings more comprehensively. Extensive experimental results demonstrate that MHADTI performs better than other SOTA prediction models. Moreover, analysis of prediction results for some interested drugs and targets further indicates that MHADTI has advantages in discovering DTIs. AVAILABILITY AND IMPLEMENTATION: https://github.com/pxystudy/MHADTI.

Long non-coding RNA(lncRNA) can interact with microRNA(miRNA) and play an important role in inhibiting or activating the expression of target genes and the occurrence and development of tumors. Accumulating studies focus on the prediction of miRNA-lncRNA interaction, and mostly are concerned with biological experiments and machine learning methods. These methods are found with long cycles, high costs, and requiring over much human intervention. In this paper, a data-driven hierarchical deep learning framework was proposed, which was composed of a capsule network, an independent recurrent neural network with attention mechanism and bi-directional long short-term memory network. This framework combines the advantages of different networks, uses multiple sequence-derived features of the original sequence and features of secondary structure to mine the dependency between features, and devotes to obtain better results. In the experiment, five-fold cross-validation was used to evaluate the performance of the model, and the zea mays data set was compared with the different model to obtain better classification effect. In addition, sorghum, brachypodium distachyon and bryophyte data sets were used to test the model, and the accuracy reached 0.9850, 0.9859 and 0.9777, respectively, which verified the model's good generalization ability.

RNA binding protein (RBP) is extensively involved in various cellular regulatory processes through the interaction with RNAs. Capturing the RBP binding preferences is fundamental for revealing the pathogenesis of complex diseases. Many experimental detection techniques are still time-consuming and labor-intensive, therefore, it is indispensable to develop a computational method with convincing accuracy. In this study, we proposed a CNN-BLSTM hybrid deep learning framework, named DeepDW, for predicting the RBP binding sites on RNAs with high-order encoding features of RNA sequence and secondary structure. The high-order encoding strategy was used to characterize the dependencies among adjacency nucleotides. For CNN-BLSTM hybrid model, DeepDW first employed two 1-D convolutional neural networks (CNNs) for learning the local features from high-order encoded matrices of RNA sequence and structure separately, and then applied two bidirectional long short-term memory networks (BLSTMs) to capture the global information in a higher level. Moreover, a series of experiments were carried out on 31 public datasets to evaluate our proposed framework, and DeepDW achieved superior performance than the state-of-the-art methods. The results indicated that the combination of high-order encoding method and CNN-BLSTM hybrid model had advantages in identifying RBP-RNA binding sites.

Recent studies have found that lncRNA (long non-coding RNA) in ncRNA (non-coding RNA) is not only involved in many biological processes, but also abnormally expressed in many complex diseases. Identification of lncRNA-disease associations accurately is of great significance for understanding the function of lncRNA and disease mechanism. In this paper, a deep learning framework consisting of stacked autoencoder(SAE), multi-scale ResNet and stacked ensemble module, named DHNLDA, was constructed to predict lncRNA-disease associations, which integrates multiple biological data sources and constructing feature matrices. Among them, the biological data including the similarity and the interaction of lncRNAs, diseases and miRNAs are integrated. The feature matrices are obtained by node2vec embedding and feature extraction respectively. Then, the SAE and the multi-scale ResNet are used to learn the complementary information between nodes, and the high-level features of node attributes are obtained. Finally, the fusion of high-level feature is input into the stacked ensemble module to obtain the prediction results of lncRNA-disease associations. The experimental results of five-fold cross-validation show that the AUC of DHNLDA reaches 0.975 better than the existing methods. Case studies of stomach cancer, breast cancer and lung cancer have shown the great ability of DHNLDA to discover the potential lncRNA-disease associations.

The interaction between ncRNA and protein is a kind of crucial molecular activities in a cell. Developing computational methods to predict ncRNA-protein interactions has attracted increasing attentions in recent years. In this work, a novel stacked ensemble learning framework is presented for predicting ncRNA-protein interaction based on heterogeneous feature combinations, named HFC-RPI. Firstly, the compositional features of k-mer with different orders were extracted from the primary sequence and secondary structure of RNA and protein respectively. Secondly, we trained a set of base learners using a variety of heterogeneous combinations of the extracted features respectively. Thirdly, the prediction results of these base learners were employed to train the stacked learner, which output the final prediction result at the higher layer in HFC-RPI. Moreover, in order to improve the generalization of HFC-RPI, when training the base learners, a cross-validation based method was applied. Extensive experimental results showed that the proposed learning framework HFC-RPI was effective and feasible for predicting the interaction of ncRNA and protein. By comparing with state-of-the-art methods, HFC-RPI was superior to them on most performance evaluation metrics.

The identification of communities is an important step in understanding of the complex network. Comparative studies suggest that the development of accurate and efficient methods to infer the communities is still in its early stages. Label propagation algorithm (LPA) that detects communities by propagating labels among vertices, attracts a great deal of attention recently. However, the communities detected by most LPAs are disjointed. Due to communities are often overlapping in real world networks, we show a multi-label propagation algorithm (MLPA) to detect overlapping communities. The inspiration is that the more people are familiar, the more they trust each other. To simulate the confidence of human communication, propagating intensity (PI) is defined to describe the confidence extent of the label propagated by neighboring vertices. The PI is then used to guide the propagation, with the purpose to make the detection more accurate. The results of extensive experiments both on synthetic and real networks show that the proposed MLPA outperforms many other methods. The effectiveness of MLPA can be attributed to its multi-label propagating strategy.

MOTIVATION: Compared with sequence and structure similarity, functional similarity is more informative for understanding the biological roles and functions of genes. Many important applications in computational molecular biology require functional similarity, such as gene clustering, protein function prediction, protein interaction evaluation and disease gene prioritization. Gene Ontology (GO) is now widely used as the basis for measuring gene functional similarity. Some existing methods combined semantic similarity scores of single term pairs to estimate gene functional similarity, whereas others compared terms in groups to measure it. However, these methods may make error-prone judgments about gene functional similarity. It remains a challenge that measuring gene functional similarity reliably. RESULT: We propose a novel method called SORA to measure gene functional similarity in GO context. First of all, SORA computes the information content (IC) of a term making use of semantic specificity and coverage. Second, SORA measures the IC of a term set by means of combining inherited and extended IC of the terms based on the structure of GO. Finally, SORA estimates gene functional similarity using the IC overlap ratio of term sets. SORA is evaluated against five state-of-the-art methods in the file on the public platform for collaborative evaluation of GO-based semantic similarity measure. The carefully comparisons show SORA is superior to other methods in general. Further analysis suggests that it primarily benefits from the structure of GO, which implies expressive information about gene function. SORA offers an effective and reliable way to compare gene function. AVAILABILITY: The web service of SORA is freely available at http://nclab.hit.edu.cn/SORA/