Multi-view attribute learning and context relationship encoding enhanced segmentation of lung tumors from CT images.

Graph convolutional neural networks (GCN) have shown the promise in medical image segmentation due to the flexibility of representing diverse range of image regions using graph nodes and propagating knowledge via graph edges. However, existing methods did not fully exploit the various attributes of image nodes and the context relationship among their attributes. We propose a new segmentation method with multi-similarity view enhancement and node attribute context learning (MNSeg). First, multiple views were formed by measuring the similarities among the image nodes, and MNSeg has a GCN based multi-view image node attribute learning (MAL) module to integrate various node attributes learnt from multiple similarity views. Each similarity view contains the specific similarities among all the image nodes, and it was integrated with the node attributes from all the channels to form the enhanced attributes of image nodes. Second, the context relationships among the attributes of image nodes are formulated by a transformer-based context relationship encoding (CRE) strategy to propagate these relationships across all the image nodes. During the transformer-based learning, the relationships were estimated based on the self-attention on all the image nodes, and then they were encoded into the learned node features. Finally, we design an attention at attribute category level (ACA) to discriminate and fuse the learnt diverse information from MAL, CRE, and the original node attributes. ACA identifies the more informative attribute categories by adaptively learn their importance. We validate the performance of MNSeg on a public lung tumor CT dataset and an in-house non-small cell lung cancer (NSCLC) dataset collected from the hospital. The segmentation results show that MNSeg outperformed the compared segmentation methods in terms of spatial overlap and the shape similarities. The ablation studies demonstrated the effectiveness of MAL, CRE, and ACA. The generalization ability of MNSeg was proved by the consistent improved segmentation performances using different 3D segmentation backbones.

Meta-Path Semantic and Global-Local Representation Learning Enhanced Graph Convolutional Model for Disease-Related miRNA Prediction.

Dysregulation of miRNAs is closely related to the progression of various diseases, so identifying disease-related miRNAs is crucial. Most recently proposed methods are based on graph reasoning, while they did not completely exploit the topological structure composed of the higher-order neighbor nodes and the global and local features of miRNA and disease nodes. We proposed a prediction method, MDAP, to learn semantic features of miRNA and disease nodes based on various meta-paths, as well as node features from the entire heterogeneous network perspective, and node pair attributes. Firstly, for both the miRNA and disease nodes, node category-wise meta-paths were constructed to integrate the similarity and association connection relationships. Each target node has its specific neighbor nodes for each meta-path, and the neighbors of longer meta-paths constitute its higher-order neighbor topological structure. Secondly, we constructed a meta-path specific graph convolutional network module to integrate the features of higher-order neighbors and their topology, and then learned the semantic representations of nodes. Thirdly, for the entire miRNA-disease heterogeneous network, a global-aware graph convolutional autoencoder was built to learn the network-view feature representations of nodes. We also designed semantic-level and representation-level attentions to obtain informative semantic features and node representations. Finally, the strategy based on the parallel convolutional-deconvolutional neural networks were designed to enhance the local feature learning for a pair of miRNA and disease nodes. The experiment results showed that MDAP outperformed other state-of-the-art methods, and the ablation experiments demonstrated the effectiveness of MDAP's major innovations. MDAP's ability in discovering potential disease-related miRNAs was further analyzed by the case studies over three diseases.

Graph reasoning method enhanced by relational transformers and knowledge distillation for drug-related side effect prediction.

Identifying the side effects related to drugs is beneficial for reducing the risk of drug development failure and saving the drug development cost. We proposed a graph reasoning method, RKDSP, to fuse the semantics of multiple connection relationships, the local knowledge within each meta-path, the global knowledge among multiple meta-paths, and the attributes of the drug and side effect node pairs. We constructed drug-side effect heterogeneous graphs consisting of the drugs, side effects, and their similarity and association connections. Multiple relational transformers were established to learn node features from diverse meta-path semantic perspectives. A knowledge distillation module was constructed to learn local and global knowledge of multiple meta-paths. Finally, an adaptive convolutional neural network-based strategy was presented to adaptively encode the attributes of each drug-side effect node pair. The experimental results demonstrated that RKDSP outperforms the compared state-of-the-art prediction approaches.

Learning Association Characteristics by Dynamic Hypergraph and Gated Convolution Enhanced Pairwise Attributes for Prediction of Disease-Related lncRNAs.

As the long non-coding RNAs (lncRNAs) play important roles during the incurrence and development of various human diseases, identifying disease-related lncRNAs can contribute to clarifying the pathogenesis of diseases. Most of the recent lncRNA-disease association prediction methods utilized the multi-source data about the lncRNAs and diseases. A single lncRNA may participate in multiple disease processes, and multiple lncRNAs usually are involved in the same disease process synergistically. However, the previous methods did not completely exploit the biological characteristics to construct the informative prediction models. We construct a prediction model based on adaptive hypergraph and gated convolution for lncRNA-disease association prediction (AGLDA), to embed and encode the biological characteristics about lncRNA-disease associations, the topological features from the entire heterogeneous graph perspective, and the gated enhanced pairwise features. First, the strategy for constructing hyperedges is designed to reflect the biological characteristic that multiple lncRNAs are involved in multiple disease processes. Furthermore, each hyperedge has its own biological perspective, and multiple hyperedges are beneficial for revealing the diverse relationships among multiple lncRNAs and diseases. Second, we encode the biological features of each lncRNA (disease) node using a strategy based on dynamic hypergraph convolutional networks. The strategy may adaptively learn the features of the hyperedges and formulate the dynamically evolved hypergraph topological structure. Third, a group convolutional network is established to integrate the entire heterogeneous topological structure and multiple types of node attributes within an lncRNA-disease-miRNA graph. Finally, a gated convolutional strategy is proposed to enhance the informative features of the lncRNA-disease node pairs. The comparison experiments indicate that AGLDA outperforms seven advanced prediction methods. The ablation studies confirm the effectiveness of major innovations, and the case studies validate AGLDA's ability in application for discovering potential disease-related lncRNA candidates.

Mutually enhanced multi-view information learning for segmentation of lung tumor in CT images.

Objective.The accurate automatic segmentation of tumors from computed tomography (CT) volumes facilitates early diagnosis and treatment of patients. A significant challenge in tumor segmentation is the integration of the spatial correlations among multiple parts of a CT volume and the context relationship across multiple channels.Approach.We proposed a mutually enhanced multi-view information model (MEMI) to propagate and fuse the spatial correlations and the context relationship and then apply it to lung tumor CT segmentation. First, a feature map was obtained from segmentation backbone encoder, which contained many image region nodes. An attention mechanism from the region node perspective was presented to determine the impact of all the other nodes on a specific node and enhance the node attribute embedding. A gated convolution-based strategy was also designed to integrate the enhanced attributes and the original node features. Second, transformer across multiple channels was constructed to integrate the channel context relationship. Finally, since the encoded node attributes from the gated convolution view and those from the channel transformer view were complementary, an interaction attention mechanism was proposed to propagate the mutual information among the multiple views.Main results.The segmentation performance was evaluated on both public lung tumor dataset and private dataset collected from a hospital. The experimental results demonstrated that MEMI was superior to other compared segmentation methods. Ablation studies showed the contributions of node correlation learning, channel context relationship learning, and mutual information interaction across multiple views to the improved segmentation performance. Utilizing MEMI on multiple segmentation backbones also demonstrated MEMI's generalization ability.Significance.Our model improved the lung tumor segmentation performance by learning the correlations among multiple region nodes, integrating the channel context relationship, and mutual information enhancement from multiple views.

Complementary feature learning across multiple heterogeneous networks and multimodal attribute learning for predicting disease-related miRNAs.

Inferring the latent disease-related miRNAs is helpful for providing a deep insight into observing the disease pathogenesis. We propose a method, CMMDA, to encode and integrate the context relationship among multiple heterogeneous networks, the complementary information across these networks, and the pairwise multimodal attributes. We first established multiple heterogeneous networks according to the diverse disease similarities. The feature representation embedding the context relationship is formulated for each miRNA (disease) node based on transformer. We designed a co-attention fusion mechanism to encode the complementary information among multiple networks. In terms of a pair of miRNA and disease nodes, the pairwise attributes from multiple networks form a multimodal attribute embedding. A module based on depthwise separable convolution is constructed to enhance the encoding of the specific features from each modality. The experimental results and the ablation studies show that CMMDA's superior performance and the effectiveness of its major innovations.

Multi-scale topology and position feature learning and relationship-aware graph reasoning for prediction of drug-related microbes.

MOTIVATION: The human microbiome may impact the effectiveness of drugs by modulating their activities and toxicities. Predicting candidate microbes for drugs can facilitate the exploration of the therapeutic effects of drugs. Most recent methods concentrate on constructing of the prediction models based on graph reasoning. They fail to sufficiently exploit the topology and position information, the heterogeneity of multiple types of nodes and connections, and the long-distance correlations among nodes in microbe-drug heterogeneous graph. RESULTS: We propose a new microbe-drug association prediction model, NGMDA, to encode the position and topological features of microbe (drug) nodes, and fuse the different types of features from neighbors and the whole heterogeneous graph. First, we formulate the position and topology features of microbe (drug) nodes by t-step random walks, and the features reveal the topological neighborhoods at multiple scales and the position of each node. Second, as the features of nodes are high-dimensional and sparse, we designed an embedding enhancement strategy based on supervised fully connected autoencoders to form the embeddings with representative features and the more discriminative node distributions. Third, we propose an adaptive neighbor feature fusion module, which fuses features of neighbors by the constructed position- and topology-sensitive heterogeneous graph neural networks. A novel self-attention mechanism is developed to estimate the importance of the position and topology of each neighbor to a target node. Finally, a heterogeneous graph feature fusion module is constructed to learn the long-distance correlations among the nodes in the whole heterogeneous graph by a relationship-aware graph transformer. Relationship-aware graph transformer contains the strategy for encoding the connection relationship types among the nodes, which is helpful for integrating the diverse semantics of these connections. The extensive comparison experimental results demonstrate NGMDA's superior performance over five state-of-the-art prediction methods. The ablation experiment shows the contributions of the multi-scale topology and position feature learning, the embedding enhancement strategy, the neighbor feature fusion, and the heterogeneous graph feature fusion. Case studies over three drugs further indicate that NGMDA has ability in discovering the potential drug-related microbes. AVAILABILITY AND IMPLEMENTATION: Source codes and Supplementary Material are available at https://github.com/pingxuan-hlju/NGMDA.

Graph Reasoning Method Based on Affinity Identification and Representation Decoupling for Predicting lncRNA-Disease Associations.

An increasing number of studies have shown that dysregulation of lncRNAs is related to the occurrence of various diseases. Most of the previous methods, however, are designed based on homogeneity assumption that the representation of a target lncRNA (or disease) node should be updated by aggregating the attributes of its neighbor nodes. However, the assumption ignores the affinity nodes that are far from the target node. We present a novel prediction method, GAIRD, to fully leverage the heterogeneous information in the network and the decoupled node features. The first major innovation is a random walk strategy based on width-first searching and depth-first searching. Different from previous methods that only focus on homogeneous information, our new strategy learns both the homogeneous information within local neighborhoods and the heterogeneous information within higher-order neighborhoods. The second innovation is a representation decoupling module to extract the purer attributes and the purer topologies. Third, a module based on group convolution and deep separable convolution is developed to promote the pairwise intrachannel and interchannel feature learning. The experimental results show that GAIRD outperforms comparing state-of-the-art methods, and the ablation studies prove the contributions of major innovations. We also performed case studies on 3 diseases to further demonstrate the effectiveness of the GAIRD model in applications.

Graph generative and adversarial strategy-enhanced node feature learning and self-calibrated pairwise attribute encoding for prediction of drug-related side effects.

Background: Inferring drug-related side effects is beneficial for reducing drug development cost and time. Current computational prediction methods have concentrated on graph reasoning over heterogeneous graphs comprising the drug and side effect nodes. However, the various topologies and node attributes within multiple drug-side effect heterogeneous graphs have not been completely exploited. Methods: We proposed a new drug-side effect association prediction method, GGSC, to deeply integrate the diverse topologies and attributes from multiple heterogeneous graphs and the self-calibration attributes of each drug-side effect node pair. First, we created two heterogeneous graphs comprising the drug and side effect nodes and their related similarity and association connections. Since each heterogeneous graph has its specific topology and node attributes, a node feature learning strategy was designed and the learning for each graph was enhanced from a graph generative and adversarial perspective. We constructed a generator based on a graph convolutional autoencoder to encode the topological structure and node attributes from the whole heterogeneous graph and then generate the node features embedding the graph topology. A discriminator based on multilayer perceptron was designed to distinguish the generated topological features from the original ones. We also designed representation-level attention to discriminate the contributions of topological representations from multiple heterogeneous graphs and adaptively fused them. Finally, we constructed a self-calibration module based on convolutional neural networks to guide pairwise attribute learning through the features of the small latent space. Results: The comparison experiment results showed that GGSC had higher prediction performance than several state-of-the-art prediction methods. The ablation experiments demonstrated the effectiveness of topological enhancement learning, representation-level attention, and self-calibrated pairwise attribute learning. In addition, case studies over five drugs demonstrated GGSC's ability in discovering the potential drug-related side effect candidates. Conclusion: We proposed a drug-side effect association prediction method, and the method is beneficial for screening the reliable association candidates for the biologists to discover the actual associations.

Learning Multi-Types of Neighbor Node Attributes and Semantics by Heterogeneous Graph Transformer and Multi-View Attention for Drug-Related Side-Effect Prediction.

Since side-effects of drugs are one of the primary reasons for their failure in clinical trials, predicting their side-effects can help reduce drug development costs. We proposed a method based on heterogeneous graph transformer and capsule networks for side-effect-drug-association prediction (TCSD). The method encodes and integrates attributes from multiple types of neighbor nodes, connection semantics, and multi-view pairwise information. In each drug-side-effect heterogeneous graph, a target node has two types of neighbor nodes, the drug nodes and the side-effect ones. We proposed a new heterogeneous graph transformer-based context representation learning module. The module is able to encode specific topology and the contextual relations among multiple kinds of nodes. There are similarity and association connections between the target node and its various types of neighbor nodes, and these connections imply semantic diversity. Therefore, we designed a new strategy to measure the importance of a neighboring node to the target node and incorporate different semantics of the connections between the target node and its multi-type neighbors. Furthermore, we designed attentions at the neighbor node type level and at the graph level, respectively, to obtain enhanced informative neighbor node features and multi-graph features. Finally, a pairwise multi-view feature learning module based on capsule networks was built to learn the pairwise attributes from the heterogeneous graphs. Our prediction model was evaluated using a public dataset, and the cross-validation results showed it achieved superior performance to several state-of-the-art methods. Ablation experiments undertaken demonstrated the effectiveness of heterogeneous graph transformer-based context encoding, the position enhanced pairwise attribute learning, and the neighborhood node category-level attention. Case studies on five drugs further showed TCSD's ability in retrieving potential drug-related side-effect candidates, and TCSD inferred the candidate side-effects for 708 drugs.

Specific topology and topological connection sensitivity enhanced graph learning for lncRNA-disease association prediction.

Predicting disease-related candidate long noncoding RNAs (lncRNAs) is beneficial for exploring disease pathogenesis due to the close relations between lncRNAs and the occurrence and development of human diseases. It is a long-term and challenging task to adequately extract specific and local topologies in individual lncRNA network and individual disease network, and integrate the information of the connection relationships. We propose a new graph learning-based prediction method to encode specific and local topologies from each individual network, neighbor topologies with different connection relationships, and pairwise attributes. We first construct a lncRNA network composed of all the lncRNA nodes and their similarities, and a single disease network that contains all the disease nodes and disease similarities. Then, a network-aware graph convolutional autoencoder is constructed to encode the specific and local topologies of each network. Secondly, a heterogeneous network is established to embed all lncRNA, disease, and miRNA nodes and their various connections. Afterwards, a connection-sensitive graph neural network is designed to deeply integrate the neighbor node attributes and connection characteristics in the heterogeneous network and learn neighbor topological representations. We also construct both connection-level and topology representation-level attention mechanisms to extract informative connections and topological representations. Finally, we build a multi-layer convolutional neural networks with weighted residuals to adaptively complement the detailed features to pairwise attribute encoding. Comprehensive experiments and comparison results demonstrated that NCPred outperforms seven state-of-the-art prediction methods. The ablation studies demonstrated the importance of local topology learning, neighbor topology learning, and pairwise attribute encoding. Case studies on prostate, lung, and breast cancers further revealed NCPred's capacity to screen potential candidate disease-related lncRNAs.

Topological structure and global features enhanced graph reasoning model for non-small cell lung cancer segmentation from CT.

Objective.Accurate and automated segmentation of lung tumors from computed tomography (CT) images is critical yet challenging. Lung tumors are of various sizes and locations and have indistinct boundaries adjacent to other normal tissues.Approach.We propose a new segmentation model that can integrate the topological structure and global features of image region nodes to address the challenges. Firstly, we construct a weighted graph with image region nodes. The graph topology reflects the complex spatial relationships among these nodes, and each node has its specific attributes. Secondly, we propose a node-wise topological feature learning module based on a new graph convolutional autoencoder (GCA). Meanwhile, a node information supplementation (GNIS) module is established by integrating specific features of each node extracted by a convolutional neural network (CNN) into each encoding layer of GCA. Afterwards, we construct a global feature extraction model based on multi-layer perceptron (MLP) to encode the features learnt from all the image region nodes which are crucial complementary information for tumor segmentation.Main results.Ablation study results over the public lung tumor segmentation dataset demonstrate the contributions of our major technical innovations. Compared with other segmentation methods, our new model improves the segmentation performance and has generalization ability on different 3D image segmentation backbones. Our model achieved Dice of 0.7827, IoU of 0.6981, and HD of 32.1743 mm on the public dataset 2018 Medical Segmentation Decathlon challenge, and Dice of 0.7004, IoU of 0.5704 and HD of 64.4661 mm on lung tumor dataset from Shandong Cancer Hospital.Significance. The novel model improves automated lung tumor segmentation performance especially the challenging and complex cases using topological structure and global features of image region nodes. It is of great potential to apply the model to other CT segmentation tasks.

Semantic Meta-Path Enhanced Global and Local Topology Learning for lncRNA-Disease Association Prediction.

Since abnormal expression of long non-coding RNAs (lncRNAs) is associated with various human diseases, identifying disease-related lncRNAs helps reveal the pathogenesis of diseases. Existing methods for lncRNA-disease association prediction mainly focus on multi-sourced data related to lncRNAs and diseases. The rich semantic information of meta-paths, composed of multiple kinds of connections between lncRNA and disease nodes, is neglected. We propose a new prediction method, MGLDA, to encode and integrate the semantics of multiple meta-paths, the global topology of heterogeneous graph, and pairwise attributes of lncRNA and disease nodes. First, a tri-layer heterogeneous graph is constructed to associate multi-sourced data across the lncRNA, disease, and miRNA nodes. Afterwards, we establish multiple meta-paths connecting the lncRNA and disease nodes to derive and denote various semantics. Each meta-path contains its specific semantics formulated by an embedding strategy, and each embedding covers local topology formed by the diverse semantic connections among the lncRNA, disease, and miRNA nodes. We construct multiple graph convolutional autoencoders (GCA) with topology-level attention to learn global and multiple local topologies from the tri-layer graph and each meta-path, respectively. The topology-level attention mechanism can learn the importance of various global and local topologies for adaptive pairwise topology fusion. Finally, a convolutional autoencoder learns the attribute representations of lncRNA-disease pairs, which integrates the learnt detailed and representative pairwise features. Experimental results show that MGLDA outperforms other state-of-the-art prediction methods in comparison and retrieves more real lncRNA-disease associations in the top-ranked candidates. The ablation study also demonstrates the important contributions of the local and global topology learning, and pairwise attribute learning. Case studies on three diseases further demonstrate MGLDA's ability to identify potential disease-related lncRNAs.

Graph based multi-scale neighboring topology deep learning for kidney and tumor segmentation.

Objective.Effective learning and modelling of spatial and semantic relations between image regions in various ranges are critical yet challenging in image segmentation tasks.Approach.We propose a novel deep graph reasoning model to learn from multi-order neighborhood topologies for volumetric image segmentation. A graph is first constructed with nodes representing image regions and graph topology to derive spatial dependencies and semantic connections across image regions. We propose a new node attribute embedding mechanism to formulate topological attributes for each image region node by performing multi-order random walks (RW) on the graph and updating neighboring topologies at different neighborhood ranges. Afterwards, multi-scale graph convolutional autoencoders are developed to extract deep multi-scale topological representations of nodes and propagate learnt knowledge along graph edges during the convolutional and optimization process. We also propose a scale-level attention module to learn the adaptive weights of topological representations at multiple scales for enhanced fusion. Finally, the enhanced topological representation and knowledge from graph reasoning are integrated with content features before feeding into the segmentation decoder.Main results.The evaluation results over public kidney and tumor CT segmentation dataset show that our model outperforms other state-of-the-art segmentation methods. Ablation studies and experiments using different convolutional neural networks backbones show the contributions of major technical innovations and generalization ability.Significance.We propose for the first time an RW-driven MCG with scale-level attention to extract semantic connections and spatial dependencies between a diverse range of regions for accurate kidney and tumor segmentation in CT volumes.

Convolutional bi-directional learning and spatial enhanced attentions for lung tumor segmentation.

BACKGROUND AND OBJECTIVE: Accurate lung tumor segmentation from computed tomography (CT) is complex due to variations in tumor sizes, shapes, patterns and growing locations. Learning semantic and spatial relations between different feature channels, image regions and positions is critical yet challenging. METHODS: We propose a new segmentation method, PRCS, by learning and integrating multi-channel contextual relations, and spatial and position dependencies across image regions. Firstly, to extract contextual relationships between different deep image feature tensor channels, we propose a new convolutional bi-directional gated recurrent unit based module for forward and backward learning. Secondly, a novel cross-channel region-level attention mechanism is proposed to discriminate the contributions of different local regions and associated features in the global learning process. Finally, spatial and position dependencies are formulated by a new position-enhanced self-attention mechanism. The new attention can measure the diverse contributions of other positions to a target position and obtain an enhanced adaptive feature vector for the target position. RESULTS: Our model outperformed seven state-of-the-art segmentation methods on both public and in-house lung tumor datasets in terms of spatial overlapping and shape similarity. Ablation study results proved the effectiveness of three technical innovations and generalization ability on different 3D CNN segmentation backbones. CONCLUSION: The proposed model enhanced the learning and propagation of contextual, spatial and position relations in 3D volumes, improving lung tumours' segmentation performance with large variations and indistinct boundaries. PRCS provides an effective automated approach to support precision diagnosis and treatment planning of lung cancer.

Learning global dependencies and multi-semantics within heterogeneous graph for predicting disease-related lncRNAs.

MOTIVATION: Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of diseases. Predicting disease-related lncRNAs can help to understand the pathogenesis of diseases deeply. The existing methods mainly rely on multi-source data related to lncRNAs and diseases when predicting the associations between lncRNAs and diseases. There are interdependencies among node attributes in a heterogeneous graph composed of all lncRNAs, diseases and micro RNAs. The meta-paths composed of various connections between them also contain rich semantic information. However, the existing methods neglect to integrate attribute information of intermediate nodes in meta-paths. RESULTS: We propose a novel association prediction model, GSMV, to learn and deeply integrate the global dependencies, semantic information of meta-paths and node-pair multi-view features related to lncRNAs and diseases. We firstly formulate the global representations of the lncRNA and disease nodes by establishing a self-attention mechanism to capture and learn the global dependencies among node attributes. Second, starting from the lncRNA and disease nodes, respectively, multiple meta-pathways are established to reveal different semantic information. Considering that each meta-path contains specific semantics and has multiple meta-path instances which have different contributions to revealing meta-path semantics, we design a graph neural network based module which consists of a meta-path instance encoding strategy and two novel attention mechanisms. The proposed meta-path instance encoding strategy is used to learn the contextual connections between nodes within a meta-path instance. One of the two new attention mechanisms is at the meta-path instance level, which learns rich and informative meta-path instances. The other attention mechanism integrates various semantic information from multiple meta-paths to learn the semantic representation of lncRNA and disease nodes. Finally, a dilated convolution-based learning module with adjustable receptive fields is proposed to learn multi-view features of lncRNA-disease node pairs. The experimental results prove that our method outperforms seven state-of-the-art comparing methods for lncRNA-disease association prediction. Ablation experiments demonstrate the contributions of the proposed global representation learning, semantic information learning, pairwise multi-view feature learning and the meta-path instance encoding strategy. Case studies on three cancers further demonstrate our method's ability to discover potential disease-related lncRNA candidates. CONTACT: zhang@hlju.edu.cn or peiliangwu@ysu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.

multi-type neighbors enhanced global topology and pairwise attribute learning for drug-protein interaction prediction.

MOTIVATION: Accurate identification of proteins interacted with drugs helps reduce the time and cost of drug development. Most of previous methods focused on integrating multisource data about drugs and proteins for predicting drug-target interactions (DTIs). There are both similarity connection and interaction connection between two drugs, and these connections reflect their relationships from different perspectives. Similarly, two proteins have various connections from multiple perspectives. However, most of previous methods failed to deeply integrate these connections. In addition, multiple drug-protein heterogeneous networks can be constructed based on multiple kinds of connections. The diverse topological structures of these networks are still not exploited completely. RESULTS: We propose a novel model to extract and integrate multi-type neighbor topology information, diverse similarities and interactions related to drugs and proteins. Firstly, multiple drug-protein heterogeneous networks are constructed according to multiple kinds of connections among drugs and those among proteins. The multi-type neighbor node sequences of a drug node (or a protein node) are formed by random walks on each network and they reflect the hidden neighbor topological structure of the node. Secondly, a module based on graph neural network (GNN) is proposed to learn the multi-type neighbor topologies of each node. We propose attention mechanisms at neighbor node level and at neighbor type level to learn more informative neighbor nodes and neighbor types. A network-level attention is also designed to enhance the context dependency among multiple neighbor topologies of a pair of drug and protein nodes. Finally, the attribute embedding of the drug-protein pair is formulated by a proposed embedding strategy, and the embedding covers the similarities and interactions about the pair. A module based on three-dimensional convolutional neural networks (CNN) is constructed to deeply integrate pairwise attributes. Extensive experiments have been performed and the results indicate GCDTI outperforms several state-of-the-art prediction methods. The recall rate estimation over the top-ranked candidates and case studies on 5 drugs further demonstrate GCDTI's ability in discovering potential drug-protein interactions.

Integrating specific and common topologies of heterogeneous graphs and pairwise attributes for drug-related side effect prediction.

MOTIVATION: Computerized methods for drug-related side effect identification can help reduce costs and speed up drug development. Multisource data about drug and side effects are widely used to predict potential drug-related side effects. Heterogeneous graphs are commonly used to associate multisourced data of drugs and side effects which can reflect similarities of the drugs from different perspectives. Effective integration and formulation of diverse similarities, however, are challenging. In addition, the specific topology of each heterogeneous graph and the common topology of multiple graphs are neglected. RESULTS: We propose a drug-side effect association prediction model, GCRS, to encode and integrate specific topologies, common topologies and pairwise attributes of drugs and side effects. First, multiple drug-side effect heterogeneous graphs are constructed using various kinds of similarities and associations related to drugs and side effects. As each heterogeneous graph has its specific topology, we establish separate module based on graph convolutional autoencoder (GCA) to learn the particular topology representation of each drug node and each side effect node, respectively. Since multiple graphs reflect the complex relationships among the drug and side effect nodes and contain common topologies, we construct a module based on GCA with sharing parameters to learn the common topology representations of each node. Afterwards, we design an attention mechanism to obtain more informative topology representations at the representation level. Finally, multi-layer convolutional neural networks with attribute-level attention are constructed to deeply integrate the similarity and association attributes of a pair of drug-side effect nodes. Comprehensive experiments show that GCRS's prediction performance is superior to other comparing state-of-the-art methods for predicting drug-side effect associations. The recall rates in top-ranked candidates and case studies on five drugs further demonstrate GCRS's ability in discovering potential drug-related side effects. CONTACT: zhang@hlju.edu.cn.

Fully connected autoencoder and convolutional neural network with attention-based method for inferring disease-related lncRNAs.

Since abnormal expression of long noncoding RNAs (lncRNAs) is often closely related to various human diseases, identification of disease-associated lncRNAs is helpful for exploring the complex pathogenesis. Most of recent methods concentrate on exploiting multiple kinds of data related to lncRNAs and diseases for predicting candidate disease-related lncRNAs. These methods, however, failed to deeply integrate the topology information from the meta-paths that are composed of lncRNA, disease and microRNA (miRNA) nodes. We proposed a new method based on fully connected autoencoders and convolutional neural networks, called ACLDA, for inferring potential disease-related lncRNA candidates. A heterogeneous graph that consists of lncRNA, disease and miRNA nodes were firstly constructed to integrate similarities, associations and interactions among them. Fully connected autoencoder-based module was established to extract the low-dimensional features of lncRNA, disease and miRNA nodes in the heterogeneous graph. We designed the attention mechanisms at the node feature level and at the meta-path level to learn more informative features and meta-paths. A module based on convolutional neural networks was constructed to encode the local topologies of lncRNA and disease nodes from multiple meta-path perspectives. The comprehensive experimental results demonstrated ACLDA achieves superior performance than several state-of-the-art prediction methods. Case studies on breast, lung and colon cancers demonstrated that ACLDA is able to discover the potential disease-related lncRNAs.

Heterogeneous multi-scale neighbor topologies enhanced drug-disease association prediction.

MOTIVATION: Identifying new uses of approved drugs is an effective way to reduce the time and cost of drug development. Recent computational approaches for predicting drug-disease associations have integrated multi-sourced data on drugs and diseases. However, neighboring topologies of various scales in multiple heterogeneous drug-disease networks have yet to be exploited and fully integrated. RESULTS: We propose a novel method for drug-disease association prediction, called MGPred, used to encode and learn multi-scale neighboring topologies of drug and disease nodes and pairwise attributes from heterogeneous networks. First, we constructed three heterogeneous networks based on multiple kinds of drug similarities. Each network comprises drug and disease nodes and edges created based on node-wise similarities and associations that reflect specific topological structures. We also propose an embedding mechanism to formulate topologies that cover different ranges of neighbors. To encode the embeddings and derive multi-scale neighboring topology representations of drug and disease nodes, we propose a module based on graph convolutional autoencoders with shared parameters for each heterogeneous network. We also propose scale-level attention to obtain an adaptive fusion of informative topological representations at different scales. Finally, a learning module based on a convolutional neural network with various receptive fields is proposed to learn multi-view attribute representations of a pair of drug and disease nodes. Comprehensive experiment results demonstrate that MGPred outperforms other state-of-the-art methods in comparison to drug-related disease prediction, and the recall rates for the top-ranked candidates and case studies on five drugs further demonstrate the ability of MGPred to retrieve potential drug-disease associations.