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In the field of cancer treatment, drug combination therapy appears to be a promising treatment strategy compared to monotherapy. Recently, plenty of computational models are gradually applied to prioritize synergistic drug combinations. However, the existing prediction models have not fully exploited the multi-way relations between drug combinations and cell lines. Besides, the number of identified drug-drug-cell line triplets is insufficient owning to the high cost of in vitro screening, which affects the ability of models to capture and utilize multi-way relations. To address this challenge, we design the multi-view hypergraph contrastive learning model, termed MHCLSyn, for synergistic drug combination prediction. First, the synergistic drug-drug-cell line triplets are formulated as a drug synergy hypergraph, and three task-specific hypergraphs are designed based on the drug synergy hypergraph. Then, we design a multi-view hypergraph contrastive learning with enhancement schemes, which allows for more expressive and discriminative node representation learning on drug synergy hypergraph. After that, the representations of nodes indicating drug-drug-cell line triplets are inputted to fully connected network for making predictions. Extensive experiments show MHCLSyn achieves better performance than state-of-the-art prediction models on benchmark datasets and is applicable to unseen drug combinations or cell lines. Case study indicates that MHCLSyn is capable of detecting potential synergistic drug combinations.

Echinococcosis is a zoonotic parasitic disease caused by the larvae of echinococcus tapeworms infesting the human body. Drug combination therapy is highly valued for the treatment of echinococcosis because of its potential to overcome resistance and enhance the response to existing drugs. Traditional methods of identifying drug combinations via biological experimentation is costly and time-consuming. Besides, the scarcity of existing drug combinations for echinococcosis hinders the development of computational methods. In this study, we propose a transfer learning-based model, namely TransferBAN-Syn, to identify synergistic drug combinations against echinococcosis based on abundant information of drug combinations against parasitic diseases. To the best of our knowledge, this is the first work that leverages transfer learning to improve prediction accuracy with limited drug combination data in echinococcosis treatment. Specifically, TransferBAN-Syn contains a drug interaction feature representation module, a disease feature representation module, and a prediction module, where the bilinear attention network is employed in the drug interaction feature representation module to deeply extract the fusion feature of drug combinations. Besides, we construct a special dataset with multi-source information and drug combinations for parasitic diseases, including 21 parasitic diseases and echinococcosis. TransferBAN-Syn is designed and initially trained on the abundant data from the 21 parasitic diseases, which serves as the source domain. The parameters in the feature representation modules of drug interactions and diseases are preserved from this source domain, and those in the prediction module are then fine-tuned to specifically identify the synergistic drug combinations for echinococcosis in the target domain. Comparison experiments have shown that TransferBAN-Syn not only improves the accuracy of predicting echinococcosis drug combinations but also enhances generalizability. Furthermore, TransferBAN-Syn identifies potential drug combinations that hold promise in the treatment of echinococcosis. TransferBAN-Syn not only offers new synergistic drug combinations for echinococcosis but also provides a novel approach for predicting potential drug pairs for diseases with limited combination data.

Interleukin-6 (IL-6) is a potent glycoprotein that plays a crucial role in regulating innate and adaptive immunity, as well as metabolism. The expression and release of IL-6 are closely correlated with the severity of various diseases. IL-6-inducing peptides are critical for the development of immunotherapy and diagnostic biomarkers for some diseases. Most existing methods for predicting IL-6-induced peptides use traditional machine learning methods, whose feature selection is based on prior knowledge. In addition, none of these methods take into account the three-dimensional (3D) structure of peptides, which is essential for their functional properties. In this study, we propose a novel IL-6-inducing peptide prediction method called DGIL-6, which integrates 3D structural information with graph neural networks. DGIL-6 represents a peptide sequence as a graph, where each amino acid is treated as a node, and the adjacency matrix, representing the relationships between nodes, is derived from the predicted residue contact graph of the peptide sequence. In addition to commonly used amino acid representations, such as one-hot encoding and position encoding, the pre-trained model ESM-1b is employed to extract amino acid features as node features. In order to simultaneously consider node weights and information updates, a dual-channel method combining Graph Attention Network (GAT) and Graph Convolutional Network (GCN) is adopted. Finally, the extracted features from both channels are merged for the classification of IL-6-inducing peptides. A series of experiments including cross-validation, independent testing, ablation studies, and visualizations demonstrate the effectiveness of the DGIL-6 method.

Abstract Since the impressive superior performance demonstrated by deep learning methods is widely used in histopathological image analysis and diagnosis, existing work cannot fully extract the information in the breast cancer images due to the limited high resolution of histopathological images. In this study, we construct a novel intermediate layer structure that fully extracts feature information and name it DMBANet, which can extract as much feature information as possible from the input image by up-dimensioning the intermediate convolutional layers to improve the performance of the network. Furthermore, we employ the depth-separable convolution method on the Spindle Structure by decoupling the intermediate convolutional layers and convolving them separately, to significantly reduce the number of parameters and computation of the Spindle Structure and improve the overall network operation speed. We also design the Spindle Structure as a multi-branch model and add different attention mechanisms to different branches. Spindle Structure can effectively improve the performance of the network, the branches with added attention can extract richer and more focused feature information, and the branch with residual connections can minimize the degradation phenomenon in our network and speed up network optimization. The comprehensive experiment shows the superior performance of DMBANet compared to the state-of-the-art method, achieving about 98% classification accuracy, which is better than existing methods. The code is available at https://github.com/Nagi-Dr/DMBANet-main .

Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer’s disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.

In recent years, numerous studies have highlighted the pivotal importance of miRNAs in personalized healthcare, showcasing broad application prospects. miRNAs hold significant potential in disease diagnosis, prognosis assessment, and therapeutic target discovery, making them an integral part of precision medicine. They are expected to enable precise disease subtyping and risk prediction, thereby advancing the development of precision medicine. GNNs, a class of deep learning architectures tailored for graph data analysis, have greatly facilitated the advancement of miRNA-disease association prediction algorithms. However, current methods often fall short in leveraging network node information, particularly in utilizing global information while neglecting the importance of local information. Effectively harnessing both local and global information remains a pressing challenge. To tackle this challenge, we propose an innovative model named DGNMDA. Initially, we constructed various miRNA and disease similarity networks based on authoritative databases. Subsequently, we creatively design a dual heterogeneous graph neural network encoder capable of efficiently learning feature information between adjacent nodes and similarity information across the entire graph. Additionally, we develop a specialized fine-grained multi-layer feature interaction gating mechanism to integrate outputs from the neural network encoders to identify novel associations connecting miRNAs with diseases. We evaluate our model using 5-fold cross-validation and real-world disease case studies, based on the HMDD V3.2 dataset. Our method demonstrates superior performance compared to existing approaches in various tasks, confirming the effectiveness and potential of DGNMDA as a robust method for predicting miRNA-disease associations.

The acurate segmentation and classification of nuclei in histological images are crucial for the diagnosis and treatment of colorectal cancer. However, the aggregation of nuclei and intra-class variability in histology images present significant challenges for nuclei segmentation and classification. In addition, the imbalance of various nuclei classes exacerbates the difficulty of nuclei classification and segmentation using deep learning models. To address these challenges, we present a novel attention-enhanced residual refinement network (AER-Net), which consists of one encoder and three decoder branches that have same network structure. In addition to the nuclei instance segmentation branch and nuclei classification branch, one branch is used to predict the vertical and horizontal distance from each pixel to its nuclear center, which is combined with output by the segmentation branch to improve the final segmentation results. The AER-Net utilizes an attention-enhanced encoder module to focus on more valuable features. To further refine predictions and achieve more accurate results, an attention-enhancing residual refinement module is employed at the end of each encoder branch. Moreover, the coarse predictions and refined predictions are combined by using a loss function that employs cross-entropy loss and generalized dice loss to efficiently tackle the challenge of class imbalance among nuclei in histology images. Compared with other state-of-the-art methods on two colorectal cancer datasets and a pan-cancer dataset, AER-Net demonstrates outstanding performance, validating its effectiveness in nuclear segmentation and classification.

Abstract Background Previous studies have identified that chromosome structure plays a very important role in gene control. The transcription factor Yin Yang 1 (YY1), a multifunctional DNA binding protein, could form a dimer to mediate chromatin loops and active enhancer-promoter interactions. The deletion of YY1 or point mutations at the YY1 binding sites significantly inhibit the enhancer-promoter interactions and affect gene expression. To date, only a few computational methods are available for identifying YY1-mediated chromatin loops. Results We proposed a novel model named CapsNetYY1, which was based on capsule network architecture to identify whether a pair of YY1 motifs can form a chromatin loop. Firstly, we encode the DNA sequence using one-hot encoding method. Secondly, multi-scale convolution layer is used to extract local features of the sequence, and bidirectional gated recurrent unit is used to learn the features across time steps. Finally, capsule networks (convolution capsule layer and digital capsule layer) used to extract higher level features and recognize YY1-mediated chromatin loops. Compared with DeepYY1, the only prediction for YY1-mediated chromatin loops, our model CapsNetYY1 achieved the better performance on the independent datasets (AUC $$> 0.99$$ > 0.99 ). Conclusion The results indicate that CapsNetYY1 is an excellent method for identifying YY1-mediated chromatin loops. We believe that the CapsNetYY1 method will be used for predictive classification of other DNA sequences.

Accumulating scientific evidence highlights the pivotal role of miRNA–disease association research in elucidating disease pathogenesis and developing innovative diagnostics. Consequently, accurately identifying disease-associated miRNAs has emerged as a prominent research topic in bioinformatics. Advances in graph neural networks (GNNs) have catalyzed methodological breakthroughs in this field. However, existing methods are often plagued by data noise and struggle to effectively integrate local and global information, which hinders their predictive performance. To address this, we introduce HGTMDA, an innovative hypergraph learning framework that incorporates random walk with restart-based association masking and an enhanced GCN-Transformer model to infer miRNA–disease associations. HGTMDA starts by constructing multiple homogeneous similarity networks. A novel enhancement of our approach is the introduction of a restart-based random walk association masking strategy. By stochastically masking a subset of association data and integrating it with a GCN enhanced by an attention mechanism, this strategy enables better capture of key information, leading to improved information utilization and reduced impact of noisy data. Next, we build an miRNA–disease heterogeneous hypergraph and adopt an improved GCN-Transformer encoder to effectively solve the effective extraction of local and global information. Lastly, we utilize a combined Dice cross-entropy (DCE) loss function to guide the model training and optimize its performance. To evaluate the performance of HGTMDA, comprehensive comparisons were conducted with state-of-the-art methods. Additionally, in-depth case studies on lung cancer and colorectal cancer were performed. The results demonstrate HGTMDA’s outstanding performance across various metrics and its exceptional effectiveness in real-world application scenarios, highlighting the advantages and value of this method.

Recent advancements in spatial transcriptomics (ST) technologies offer unprecedented opportunities to unveil the spatial heterogeneity of gene expression and cell states within tissues. Despite these capabilities of the ST data, accurately dissecting spatiotemporal structures (e.g., spatial domains, temporal trajectories, and functional interactions) remains challenging. Here, we introduce a computational framework, PearlST (partial differential equation [PDE]-enhanced adversarial graph autoencoder of ST), for accurate inference of spatiotemporal structures from the ST data using PDE-enhanced adversarial graph autoencoder. PearlST employs contrastive learning to extract histological image features, integrates a PDE-based diffusion model to enhance characterization of spatial features at domain boundaries, and learns the latent low-dimensional embeddings via Wasserstein adversarial regularized graph autoencoders. Comparative analyses across multiple ST datasets with varying resolutions demonstrate that PearlST outperforms existing methods in spatial clustering, trajectory inference, and pseudotime analysis. Furthermore, PearlST elucidates functional regulations of the latent features by linking intercellular ligand–receptor interactions to most contributing genes of the low-dimensional embeddings, as illustrated in a human breast cancer dataset. Overall, PearlST proves to be a powerful tool for extracting interpretable latent features and dissecting intricate spatiotemporal structures in ST data across various biological contexts.

Abstract Background Single-cell RNA sequencing (scRNA-seq) strives to capture cellular diversity with higher resolution than bulk RNA sequencing. Clustering analysis is critical to transcriptome research as it allows for further identification and discovery of new cell types. Unsupervised clustering cannot integrate prior knowledge where relevant information is widely available. Purely unsupervised clustering algorithms may not yield biologically interpretable clusters when confronted with the high dimensionality of scRNA-seq data and frequent dropout events, which makes identification of cell types more challenging. Results We propose scSemiAAE, a semi-supervised clustering model for scRNA sequence analysis using deep generative neural networks. Specifically, scSemiAAE carefully designs a ZINB adversarial autoencoder-based architecture that inherently integrates adversarial training and semi-supervised modules in the latent space. In a series of experiments on scRNA-seq datasets spanning thousands to tens of thousands of cells, scSemiAAE can significantly improve clustering performance compared to dozens of unsupervised and semi-supervised algorithms, promoting clustering and interpretability of downstream analyses. Conclusion scSemiAAE is a Python-based algorithm implemented on the VSCode platform that provides efficient visualization, clustering, and cell type assignment for scRNA-seq data. The tool is available from https://github.com/WHang98/scSemiAAE .

Cancer is a complex and evolutionary disease mainly driven by the accumulation of genetic variations in genes. Identifying cancer driver genes is important. However, most related studies have focused on the population level. Cancer is a disease with high heterogeneity. Thus, the discovery of driver genes at the individual level is becoming more valuable but is a great challenge. Although there have been some computational methods proposed to tackle this challenge, few can cover all patient samples well, and there is still room for performance improvement. In this study, to identify individual-level driver genes more efficiently, we propose the PDGCN method. PDGCN integrates multiple types of data features, including mutation, expression, methylation, copy number data, and system-level gene features, along with network structural features extracted using Node2vec in order to construct a sample–gene interaction network. Prediction is performed using a graphical convolutional neural network model with a conditional random field layer, which is able to better combine the network structural features with biological attribute features. Experiments on the ACC (Adrenocortical Cancer) and KICH (Kidney Chromophobe) datasets from TCGA (The Cancer Genome Atlas) demonstrated that the method performs better compared to other similar methods. It can identify not only frequently mutated driver genes, but also rare candidate driver genes and novel biomarker genes. The results of the survival and enrichment analyses of these detected genes demonstrate that the method can identify important driver genes at the individual level.

Medical image segmentation plays a crucial role in clinical diagnosis, treatment planning, and disease monitoring. The automatic segmentation method based on deep learning has developed rapidly, with segmentation results comparable to clinical experts for large objects, but the segmentation accuracy for small objects is still unsatisfactory. Current segmentation methods based on deep learning find it difficult to extract multiple scale features of medical images, leading to an insufficient detection capability for smaller objects. In this paper, we propose a context feature fusion and attention mechanism based network for small target segmentation in medical images called CFANet. CFANet is based on U-Net structure, including the encoder and the decoder, and incorporates two key modules, context feature fusion (CFF) and effective channel spatial attention (ECSA), in order to improve segmentation performance. The CFF module utilizes contextual information from different scales to enhance the representation of small targets. By fusing multi-scale features, the network captures local and global contextual cues, which are critical for accurate segmentation. The ECSA module further enhances the network’s ability to capture long-range dependencies by incorporating attention mechanisms at the spatial and channel levels, which allows the network to focus on information-rich regions while suppressing irrelevant or noisy features. Extensive experiments are conducted on four challenging medical image datasets, namely ADAM, LUNA16, Thoracic OAR, and WORD. Experimental results show that CFANet outperforms state-of-the-art methods in terms of segmentation accuracy and robustness. The proposed method achieves excellent performance in segmenting small targets in medical images, demonstrating its potential in various clinical applications.

Single cell RNA sequencing (scRNA-seq) enables researchers to characterize transcriptomic profiles at the single-cell resolution with increasingly high throughput. Clustering is a crucial step in single cell analysis. Clustering analysis of transcriptome profiled by scRNA-seq can reveal the heterogeneity and diversity of cells. However, single cell study still remains great challenges due to its high noise and dimension. Subspace clustering aims at discovering the intrinsic structure of data in unsupervised fashion. In this paper, we propose a deep sparse subspace clustering method scDSSC combining noise reduction and dimensionality reduction for scRNA-seq data, which simultaneously learns feature representation and clustering via explicit modelling of scRNA-seq data generation. Experiments on a variety of scRNA-seq datasets from thousands to tens of thousands of cells have shown that scDSSC can significantly improve clustering performance and facilitate the interpretability of clustering and downstream analysis. Compared to some popular scRNA-deq analysis methods, scDSSC outperformed state-of-the-art methods under various clustering performance metrics.

Abstract Background In recent years, various sequencing techniques have been used to collect biomedical omics datasets. It is usually possible to obtain multiple types of omics data from a single patient sample. Clustering of omics data plays an indispensable role in biological and medical research, and it is helpful to reveal data structures from multiple collections. Nevertheless, clustering of omics data consists of many challenges. The primary challenges in omics data analysis come from high dimension of data and small size of sample. Therefore, it is difficult to find a suitable integration method for structural analysis of multiple datasets. Results In this paper, a multi-view clustering based on Stiefel manifold method (MCSM) is proposed. The MCSM method comprises three core steps. Firstly, we established a binary optimization model for the simultaneous clustering problem. Secondly, we solved the optimization problem by linear search algorithm based on Stiefel manifold. Finally, we integrated the clustering results obtained from three omics by using k-nearest neighbor method. We applied this approach to four cancer datasets on TCGA. The result shows that our method is superior to several state-of-art methods, which depends on the hypothesis that the underlying omics cluster class is the same. Conclusion Particularly, our approach has better performance than compared approaches when the underlying clusters are inconsistent. For patients with different subtypes, both consistent and differential clusters can be identified at the same time.

Abstract Background Deep learning algorithms significantly improve the accuracy of pathological image classification, but the accuracy of breast cancer classification using only single-mode pathological images still cannot meet the needs of clinical practice. Inspired by the real scenario of pathologists reading pathological images for diagnosis, we integrate pathological images and structured data extracted from clinical electronic medical record (EMR) to further improve the accuracy of breast cancer classification. Methods In this paper, we propose a new richer fusion network for the classification of benign and malignant breast cancer based on multimodal data. To make pathological image can be integrated more sufficient with structured EMR data, we proposed a method to extract richer multilevel feature representation of the pathological image from multiple convolutional layers. Meanwhile, to minimize the information loss for each modality before data fusion, we use the denoising autoencoder as a way to increase the low-dimensional structured EMR data to high-dimensional, instead of reducing the high-dimensional image data to low-dimensional before data fusion. In addition, denoising autoencoder naturally generalizes our method to make the accurate prediction with partially missing structured EMR data. Results The experimental results show that the proposed method is superior to the most advanced method in terms of the average classification accuracy (92.9%). In addition, we have released a dataset containing structured data from 185 patients that were extracted from EMR and 3764 paired pathological images of breast cancer, which can be publicly downloaded from http://ear.ict.ac.cn/?page_id=1663 . Conclusions We utilized a new richer fusion network to integrate highly heterogeneous data to leverage the structured EMR data to improve the accuracy of pathological image classification. Therefore, the application of automatic breast cancer classification algorithms in clinical practice becomes possible. Due to the generality of the proposed fusion method, it can be straightforwardly extended to the fusion of other structured data and unstructured data.

Abstract Background The recognition of protein interaction sites is of great significance in many biological processes, signaling pathways and drug designs. However, most sites on protein sequences cannot be defined as interface or non-interface sites because only a small part of protein interactions had been identified, which will cause the lack of prediction accuracy and generalization ability of predictors in protein interaction sites prediction. Therefore, it is necessary to effectively improve prediction performance of protein interaction sites using large amounts of unlabeled data together with small amounts of labeled data and background knowledge today. Results In this work, three semi-supervised support vector machine–based methods are proposed to improve the performance in the protein interaction sites prediction, in which the information of unlabeled protein sites can be involved. Herein, five features related with the evolutionary conservation of amino acids are extracted from HSSP database and Consurf Sever, i.e., residue spatial sequence spectrum, residue sequence information entropy and relative entropy, residue sequence conserved weight and residual Base evolution rate, to represent the residues within the protein sequence. Then three predictors are built for identifying the interface residues from protein surface using three types of semi-supervised support vector machine algorithms. Conclusion The experimental results demonstrated that the semi-supervised approaches can effectively improve prediction performance of protein interaction sites when unlabeled information is involved into the predictors and one of them can achieve the best prediction performance, i.e., the accuracy of 70.7%, the sensitivity of 62.67% and the specificity of 78.72%, respectively. With comparison to the existing studies, the semi-supervised models show the improvement of the predication performance.

Dimensionality reduction of high-dimensional data is crucial for single-cell RNA sequencing (scRNA-seq) visualization and clustering. One prominent challenge in scRNA-seq studies comes from the dropout events, which lead to zero-inflated data. To address this issue, in this paper, we propose a scRNA-seq data dimensionality reduction algorithm based on a hierarchical autoencoder, termed SCDRHA. The proposed SCDRHA consists of two core modules, where the first module is a deep count autoencoder (DCA) that is used to denoise data, and the second module is a graph autoencoder that projects the data into a low-dimensional space. Experimental results demonstrate that SCDRHA has better performance than existing state-of-the-art algorithms on dimension reduction and noise reduction in five real scRNA-seq datasets. Besides, SCDRHA can also dramatically improve the performance of data visualization and cell clustering.

Radiotherapy plays an important role in controlling the local recurrence of esophageal cancer after radical surgery. Segmentation of the clinical target volume is a key step in radiotherapy treatment planning, but it is time-consuming and operator-dependent. This paper introduces a deep dilated convolutional U-network to achieve fast and accurate clinical target volume auto-segmentation of esophageal cancer after radical surgery. The deep dilated convolutional U-network, which integrates the advantages of dilated convolution and the U-network, is an end-to-end architecture that enables rapid training and testing. A dilated convolution module for extracting multiscale context features containing the original information on fine texture and boundaries is integrated into the U-network architecture to avoid information loss due to down-sampling and improve the segmentation accuracy. In addition, batch normalization is added to the deep dilated convolutional U-network for fast and stable convergence. In the present study, the training and validation loss tended to be stable after 40 training epochs. This deep dilated convolutional U-network model was able to segment the clinical target volume with an overall mean Dice similarity coefficient of 86.7% and a respective 95% Hausdorff distance of 37.4 mm, indicating reasonable volume overlap of the auto-segmented and manual contours. The mean Cohen kappa coefficient was 0.863, indicating that the deep dilated convolutional U-network was robust. Comparisons with the U-network and attention U-network showed that the overall performance of the deep dilated convolutional U-network was best for the Dice similarity coefficient, 95% Hausdorff distance, and Cohen kappa coefficient. The test time for segmentation of the clinical target volume was approximately 25 seconds per patient. This deep dilated convolutional U-network could be applied in the clinical setting to save time in delineation and improve the consistency of contouring.

In recent years, more and more evidence has shown that microRNAs (miRNAs) play an important role in the regulation of post-transcriptional gene expression, and are closely related to human diseases. Many studies have also revealed that miRNAs can be served as promising biomarkers for the potential diagnosis and treatment of human diseases. The interactions between miRNA and human disease have rarely been demonstrated, and the underlying mechanism of miRNA is not clear. Therefore, computational approaches has attracted the attention of researchers, which can not only save time and money, but also improve the efficiency and accuracy of biological experiments. In this work, we proposed a Heterogeneous Graph Attention Networks (GAT) based method for miRNA-disease associations prediction, named HGATMDA. We constructed a heterogeneous graph for miRNAs and diseases, introduced weighted DeepWalk and GAT methods to extract features of miRNAs and diseases from the graph. Moreover, a fully-connected neural networks is used to predict correlation scores between miRNA-disease pairs. Experimental results under five-fold cross validation (five-fold CV) showed that HGATMDA achieved better prediction performance than other state-of-the-art methods. In addition, we performed three case studies on breast neoplasms, lung neoplasms and kidney neoplasms. The results showed that for the three diseases mentioned above, 50 out of top 50 candidates were confirmed by the validation datasets. Therefore, HGATMDA is suitable as an effective tool to identity potential diseases-related miRNAs.

An emerging type of therapeutic agent, anticancer peptides (ACPs), has attracted attention because of its lower risk of toxic side effects. However process of identifying ACPs using experimental methods is both time-consuming and laborious. In this study, we developed a new and efficient algorithm that predicts ACPs by fusing multi-view features based on dual-channel deep neural network ensemble model. In the model, one channel used the convolutional neural network CNN to automatically extract the potential spatial features of a sequence. Another channel was used to process and extract more effective features from handcrafted features. Additionally, an effective feature fusion method was explored for the mutual fusion of different features. Finally, we adopted the neural network to predict ACPs based on the fusion features. The performance comparisons across the single and fusion features showed that the fusion of multi-view features could effectively improve the model’s predictive ability. Among these, the fusion of the features extracted by the CNN and composition of k-spaced amino acid group pairs achieved the best performance. To further validate the performance of our model, we compared it with other existing methods using two independent test sets. The results showed that our model’s area under curve was 0.90, which was higher than that of the other existing methods on the first test set and higher than most of the other existing methods on the second test set. The source code and datasets are available at https://github.com/wame-ng/DLFF-ACP.

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules, which have many biological functions. Previous experiments have shown that circRNAs are involved in numerous biological processes, especially regulatory functions. It has also been found that circRNAs are associated with complex diseases of human beings. Therefore, predicting the associations of circRNA with disease (called circRNA-disease associations) is useful for disease prevention, diagnosis and treatment. In this work, we propose a novel computational approach called GGCDA based on the Graph Attention Network (GAT) and Graph Convolutional Network (GCN) to predict circRNA-disease associations. Firstly, GGCDA combines circRNA sequence similarity, disease semantic similarity and corresponding Gaussian interaction profile kernel similarity, and then a random walk with restart algorithm (RWR) is used to obtain the preliminary features of circRNA and disease. Secondly, a heterogeneous graph is constructed from the known circRNA-disease association network and the calculated similarity of circRNAs and diseases. Thirdly, the multi-head Graph Attention Network (GAT) is adopted to obtain different weights of circRNA and disease features, and then GCN is employed to aggregate the features of adjacent nodes in the network and the features of the nodes themselves, so as to obtain multi-view circRNA and disease features. Finally, we combined a multi-layer fully connected neural network to predict the associations of circRNAs with diseases. In comparison with state-of-the-art methods, GGCDA can achieve AUC values of 0.9625 and 0.9485 under the results of fivefold cross-validation on two datasets, and AUC of 0.8227 on the independent test set. Case studies further demonstrate that our approach is promising for discovering potential circRNA-disease associations.

Accumulating biological and clinical evidence has confirmed the important associations between microRNAs (miRNAs) and a variety of human diseases. Predicting disease-related miRNAs is beneficial for understanding the molecular mechanisms of pathological conditions at the miRNA level, and facilitating the finding of new biomarkers for prevention, diagnosis and treatment of complex human diseases. However, the challenge for researchers is to establish methods that can effectively combine different datasets and make reliable predictions. In this work, we propose the method of Multi-Similarity based Combinative Hypergraph Learning for Predicting MiRNA-disease Association (MSCHLMDA). To establish this method, complex features were extracted by two measures for each miRNA-disease pair. Then, K-nearest neighbor (KNN) and K-means algorithm were used to construct two different hypergraphs. Finally, results from combinative hypergraph learning were used for predicting miRNA-disease association. In order to evaluate the prediction performance of our method, leave-one-out cross validation and 5-fold cross validation was implemented, showing that our method had significantly improved prediction performance compared to previously used methods. Moreover, three case studies on different human complex diseases were performed, which further demonstrated the predictive performance of MSCHLMDA. It is anticipated that MSCHLMDA would become an excellent complement to the biomedical research field in the future.

Since pathological images have some distinct characteristics that are different from natural images, the direct application of a general convolutional neural network cannot achieve good classification performance, especially for fine-grained classification problems (such as pathological image grading). Inspired by the clinical experience that decomposing a pathological image into different components is beneficial for diagnosis, in this paper, we propose a Divide-and-Attention Network (DANet) for Hematoxylin-and-Eosin (HE)-stained pathological image classification. The DANet utilizes a deep-learning method to decompose a pathological image into nuclei and non-nuclei parts. With such decomposed pathological images, the DANet first performs feature learning independently in each branch, and then focuses on the most important feature representation through the branch selection attention module. In this way, the DANet can learn representative features with respect to different tissue structures and adaptively focus on the most important ones, thereby improving classification performance. In addition, we introduce deep canonical correlation analysis (DCCA) constraints in the feature fusion process of different branches. The DCCA constraints play the role of branch fusion attention, so as to maximize the correlation of different branches and ensure that the fused branches emphasize specific tissue structures. The experimental results of three datasets demonstrate the superiority of the DANet, with an average classification accuracy of 92.5% on breast cancer classification, 95.33% on colorectal cancer grading, and 91.6% on breast cancer grading tasks.

Breast cancer grading methods based on hematoxylin-eosin (HE) stained pathological images can be summarized into two categories. The first category is to directly extract the pathological image features for breast cancer grading. However, unlike the coarse-grained problem of breast cancer classification, breast cancer grading is a fine-grained classification problem, so general methods cannot achieve satisfactory results. The second category is to apply the three evaluation criteria of the Nottingham Grading System (NGS) separately, and then integrate the results of the three criteria to obtain the final grading result. However, NGS is only a semiquantitative evaluation method, and there may be far more image features related to breast cancer grading. In this paper, we proposed a Nuclei-Guided Network (NGNet) for breast invasive ductal carcinoma (IDC) grading in pathological images. The proposed nuclei-guided attention module plays the role of nucleus attention, so as to learn more nuclei-related feature representations for breast IDC grading. In addition, the proposed nuclei-guided fusion module in the fusion process of different branches can further enable the network to focus on learning nuclei-related features. Overall, under the guidance of nuclei-related features, the entire NGNet can learn more fine-grained features for breast IDC grading. The experimental results show that the performance of the proposed method is better than that of state-of-the-art method. In addition, we released a well-labeled dataset with 3644 pathological images for breast IDC grading. This dataset is currently the largest publicly available breast IDC grading dataset and can serve as a benchmark to facilitate a broader study of breast IDC grading.

As an important approach to cancer classification, cancer sample clustering is of particular importance for cancer research. For high dimensional gene expression data, examining approaches to selecting characteristic genes with high identification for cancer sample clustering is an important research area in the bioinformatics field. In this paper, we propose a novel integrated framework for cancer clustering known as the non-negative symmetric low-rank representation with graph regularization based on score function (NSLRG-S). First, a lowest rank matrix is obtained after NSLRG decomposition. The lowest rank matrix preserves the local data manifold information and the global data structure information of the gene expression data. Second, we construct the Score function based on the lowest rank matrix to weight all of the features of the gene expression data and calculate the score of each feature. Third, we rank the features according to their scores and select the feature genes for cancer sample clustering. Finally, based on selected feature genes, we use the K-means method to cluster the cancer samples. The experiments are conducted on The Cancer Genome Atlas (TCGA) data. Comparative experiments demonstrate that the NSLRG-S framework can significantly improve the clustering performance.

Hyperspectral image (HSI) clustering has drawn increasing attention due to its challenging work with respect to the curse of dimensionality. In this paper, we propose a novel class probability propagation of supervised information based on sparse subspace clustering (CPPSSC) algorithm for HSI clustering. Firstly, we estimate the class probability of unlabeled samples by way of partial known supervised information, which can be addressed by sparse representation-based classification (SRC). Then, we incorporate the class probability into the traditional sparse subspace clustering (SSC) model to obtain a more accurate sparse representation coefficient matrix accompanied by obvious block diagonalization, which will be used to build the similarity matrix. Finally, the cluster results can be obtained by applying the spectral clustering on similarity matrix. Extensive experiments on a variety of challenging data sets illustrate that our proposed method is effective.