HGCLAMIR: Hypergraph contrastive learning with attention mechanism and integrated multi-view representation for predicting miRNA-disease associations.

Existing studies have shown that the abnormal expression of microRNAs (miRNAs) usually leads to the occurrence and development of human diseases. Identifying disease-related miRNAs contributes to studying the pathogenesis of diseases at the molecular level. As traditional biological experiments are time-consuming and expensive, computational methods have been used as an effective complement to infer the potential associations between miRNAs and diseases. However, most of the existing computational methods still face three main challenges: (i) learning of high-order relations; (ii) insufficient representation learning ability; (iii) importance learning and integration of multi-view embedding representation. To this end, we developed a HyperGraph Contrastive Learning with view-aware Attention Mechanism and Integrated multi-view Representation (HGCLAMIR) model to discover potential miRNA-disease associations. First, hypergraph convolutional network (HGCN) was utilized to capture high-order complex relations from hypergraphs related to miRNAs and diseases. Then, we combined HGCN with contrastive learning to improve and enhance the embedded representation learning ability of HGCN. Moreover, we introduced view-aware attention mechanism to adaptively weight the embedded representations of different views, thereby obtaining the importance of multi-view latent representations. Next, we innovatively proposed integrated representation learning to integrate the embedded representation information of multiple views for obtaining more reasonable embedding information. Finally, the integrated representation information was fed into a neural network-based matrix completion method to perform miRNA-disease association prediction. Experimental results on the cross-validation set and independent test set indicated that HGCLAMIR can achieve better prediction performance than other baseline models. Furthermore, the results of case studies and enrichment analysis further demonstrated the accuracy of HGCLAMIR and unconfirmed potential associations had biological significance.

Predicting potential microbe-disease associations based on auto-encoder and graph convolution network.

The increasing body of research has consistently demonstrated the intricate correlation between the human microbiome and human well-being. Microbes can impact the efficacy and toxicity of drugs through various pathways, as well as influence the occurrence and metastasis of tumors. In clinical practice, it is crucial to elucidate the association between microbes and diseases. Although traditional biological experiments accurately identify this association, they are time-consuming, expensive, and susceptible to experimental conditions. Consequently, conducting extensive biological experiments to screen potential microbe-disease associations becomes challenging. The computational methods can solve the above problems well, but the previous computational methods still have the problems of low utilization of node features and the prediction accuracy needs to be improved. To address this issue, we propose the DAEGCNDF model predicting potential associations between microbes and diseases. Our model calculates four similar features for each microbe and disease. These features are fused to obtain a comprehensive feature matrix representing microbes and diseases. Our model first uses the graph convolutional network module to extract low-rank features with graph information of microbes and diseases, and then uses a deep sparse Auto-Encoder to extract high-rank features of microbe-disease pairs, after which the low-rank and high-rank features are spliced to improve the utilization of node features. Finally, Deep Forest was used for microbe-disease potential relationship prediction. The experimental results show that combining low-rank and high-rank features helps to improve the model performance and Deep Forest has better classification performance than the baseline model.

Inferring circRNA-drug sensitivity associations via dual hierarchical attention networks and multiple kernel fusion.

Increasing evidence has shown that the expression of circular RNAs (circRNAs) can affect the drug sensitivity of cells and significantly influence drug efficacy. Therefore, research into the relationships between circRNAs and drugs can be of great significance in increasing the comprehension of circRNAs function, as well as contributing to the discovery of new drugs and the repurposing of existing drugs. However, it is time-consuming and costly to validate the function of circRNA with traditional medical research methods. Therefore, the development of efficient and accurate computational models that can assist in discovering the potential interactions between circRNAs and drugs is urgently needed. In this study, a novel method is proposed, called DHANMKF , that aims to predict potential circRNA-drug sensitivity interactions for further biomedical screening and validation. Firstly, multimodal networks were constructed by DHANMKF using multiple sources of information on circRNAs and drugs. Secondly, comprehensive intra-type and inter-type node representations were learned using bi-typed multi-relational heterogeneous graphs, which are attention-based encoders utilizing a hierarchical process. Thirdly, the multi-kernel fusion method was used to fuse intra-type embedding and inter-type embedding. Finally, the Dual Laplacian Regularized Least Squares method (DLapRLS) was used to predict the potential circRNA-drug sensitivity associations using the combined kernel in circRNA and drug spaces. Compared with the other methods, DHANMKF obtained the highest AUC value on two datasets. Code is available at https://github.com/cuntjx/DHANMKF .

Self-supervised learning-based Multi-Scale feature Fusion Network for survival analysis from whole slide images.

Understanding prognosis and mortality is critical for evaluating the treatment plan of patients. Advances in digital pathology and deep learning techniques have made it practical to perform survival analysis in whole slide images (WSIs). Current methods are usually based on a multi-stage framework which includes patch sampling, feature extraction and prediction. However, the random patch sampling strategy is highly unstable and prone to sampling non-ROI. Feature extraction typically relies on hand-crafted features or convolutional neural networks (CNNs) pre-trained on ImageNet, while the artificial error or domain gaps may affect the survival prediction performance. Besides, the limited information representation of local sampling patches will create a bottleneck limitation on the effectiveness of prediction. To address the above challenges, we propose a novel patch sampling strategy based on image information entropy and construct a Multi-Scale feature Fusion Network (MSFN) based on self-supervised feature extractor. Specifically, we adopt image information entropy as a criterion to select representative sampling patches, thereby avoiding the noise interference caused by random to blank regions. Meanwhile, we pretrain the feature extractor utilizing self-supervised learning mechanism to improve the efficiency of feature extraction. Furthermore, a global-local feature fusion prediction network based on the attention mechanism is constructed to improve the survival prediction effect of WSIs with comprehensive multi-scale information representation. The proposed method is validated by adequate experiments and achieves competitive results on both of the most popular WSIs survival analysis datasets, TCGA-GBM and TCGA-LUSC. Code and trained models are made available at: https://github.com/Mercuriiio/MSFN.

Integration of multi-omics data using adaptive graph learning and attention mechanism for patient classification and biomarker identification.

With the rapid development and accumulation of high-throughput sequencing technology and omics data, many studies have conducted a more comprehensive understanding of human diseases from a multi-omics perspective. Meanwhile, graph-based methods have been widely used to process multi-omics data due to its powerful expressive ability. However, most existing graph-based methods utilize fixed graphs to learn sample embedding representations, which often leads to sub-optimal results. Furthermore, treating embedding representations of different omics equally usually cannot obtain more reasonable integrated information. In addition, the complex correlation between omics is not fully taken into account. To this end, we propose an end-to-end interpretable multi-omics integration method, named MOGLAM, for disease classification prediction. Dynamic graph convolutional network with feature selection is first utilized to obtain higher quality omic-specific embedding information by adaptively learning the graph structure and discover important biomarkers. Then, multi-omics attention mechanism is applied to adaptively weight the embedding representations of different omics, thereby obtaining more reasonable integrated information. Finally, we propose omic-integrated representation learning to capture complex common and complementary information between omics while performing multi-omics integration. Experimental results on three datasets show that MOGLAM achieves superior performance than other state-of-the-art multi-omics integration methods. Moreover, MOGLAM can identify important biomarkers from different omics data types in an end-to-end manner.

Inferring human miRNA-disease associations via multiple kernel fusion on GCNII.

Increasing evidence shows that the occurrence of human complex diseases is closely related to the mutation and abnormal expression of microRNAs(miRNAs). MiRNAs have complex and fine regulatory mechanisms, which makes it a promising target for drug discovery and disease diagnosis. Therefore, predicting the potential miRNA-disease associations has practical significance. In this paper, we proposed an miRNA-disease association predicting method based on multiple kernel fusion on Graph Convolutional Network via Initial residual and Identity mapping (GCNII), called MKFGCNII. Firstly, we built a heterogeneous network of miRNAs and diseases to extract multi-layer features via GCNII. Secondly, multiple kernel fusion method was applied to weight fusion of embeddings at each layer. Finally, Dual Laplacian Regularized Least Squares was used to predict new miRNA-disease associations by the combined kernel in miRNA and disease spaces. Compared with the other methods, MKFGCNII obtained the highest AUC value of 0.9631. Code is available at https://github.com/cuntjx/bioInfo.