MicroRNAs (miRNA) are endogenous non-coding RNAs, typically around 23 nucleotides in length. Many miRNAs have been founded to play crucial roles in gene regulation though post-transcriptional repression in animals. Existing studies suggest that the dysregulation of miRNA is closely associated with many human diseases. Discovering novel associations between miRNAs and diseases is essential for advancing our understanding of disease pathogenesis at molecular level. However, experimental validation is time-consuming and expensive. To address this challenge, numerous computational methods have been proposed for predicting miRNA-disease associations. Unfortunately, most existing methods face difficulties when applied to large-scale miRNA-disease complex networks. In this paper, we present a novel subgraph learning method named SGLMDA for predicting miRNA-disease associations. For miRNA-disease pairs, SGLMDA samples K-hop subgraphs from the global heterogeneous miRNA-disease graph. It then introduces a novel subgraph representation algorithm based on Graph Neural Network (GNN) for feature extraction and prediction. Extensive experiments conducted on benchmark datasets demonstrate that SGLMDA can effectively and robustly predict potential miRNA-disease associations. Compared to other state-of-the-art methods, SGLMDA achieves superior prediction performance in terms of Area Under the Curve (AUC) and Average Precision (AP) values during 5-fold Cross-Validation (5CV) on benchmark datasets such as HMDD v2.0 and HMDD v3.2. Additionally, case studies on Colon Neoplasms and Triple-Negative Breast Cancer (TNBC) further underscore the predictive power of SGLMDA.

Rapid advances in single-cell RNA sequencing (scRNA-seq) have made it possible to characterize cell states at a high resolution view for large scale library. scRNA-seq data contains a great deal of biological information, which can be mainly used to discover cell subtypes and track cell development. However, traditional methods face many challenges in addressing scRNA-seq data with high dimensions and high sparsity. For better analysis of scRNA-seq data, we propose a new framework called MSVGAE based on variational graph auto-encoder and graph attention networks. Specifically, we introduce multiple encoders to learn features at different scales and control for uninformative features. Moreover, different noises are added to encoders to promote the propagation of graph structural information and distribution uncertainty. Therefore, some complex posterior distributions can be captured by our model. MSVGAE maps scRNA-seq data with high dimensions and high noise into the low-dimensional latent space, which is beneficial for downstream tasks. In particular, MSVGAE can handle extremely sparse data. Before the experiment, we create 24 simulated datasets to simulate various biological scenarios and collect 8 real-world datasets. The experimental results of clustering, visualization and marker genes analysis indicate that MSVGAE model has excellent accuracy and robustness in analyzing scRNA-seq data.

CircRNAs have a stable structure, which gives them a higher tolerance to nucleases. Therefore, the properties of circular RNAs are beneficial in disease diagnosis. However, there are few known associations between circRNAs and disease. Biological experiments identify new associations is time-consuming and high-cost. As a result, there is a need of building efficient and achievable computation models to predict potential circRNA-disease associations. In this paper, we design a novel convolution neural networks framework(DMFCNNCD) to learn features from deep matrix factorization to predict circRNA-disease associations. Firstly, we decompose the circRNA-disease association matrix to obtain the original features of the disease and circRNA, and use the mapping module to extract potential nonlinear features. Then, we integrate it with the similarity information to form a training set. Finally, we apply convolution neural networks to predict the unknown association between circRNAs and diseases. The five-fold cross-validation on various experiments shows that our method can predict circRNA-disease association and outperforms state of the art methods.

Single-cell RNA sequencing (scRNA-seq) has rapidly emerged as a powerful technique for analyzing cellular heterogeneity at the individual cell level. In the analysis of scRNA-seq data, cell clustering is a critical step in downstream analysis, as it enables the identification of cell types and the discovery of novel cell subtypes. However, the characteristics of scRNA-seq data, such as high dimensionality and sparsity, dropout events and batch effects, present significant computational challenges for clustering analysis. In this study, we propose scGCC, a novel graph self-supervised contrastive learning model, to address the challenges faced in scRNA-seq data analysis. scGCC comprises two main components: a representation learning module and a clustering module. The scRNA-seq data is first fed into a representation learning module for training, which is then used for data classification through a clustering module. scGCC can learn low-dimensional denoised embeddings, which is advantageous for our clustering task. We introduce Graph Attention Networks (GAT) for cell representation learning, which enables better feature extraction and improved clustering accuracy. Additionally, we propose five data augmentation methods to improve clustering performance by increasing data diversity and reducing overfitting. These methods enhance the robustness of clustering results. Our experimental study on 14 real-world datasets has demonstrated that our model achieves extraordinary accuracy and robustness. We also perform downstream tasks, including batch effect removal, trajectory inference, and marker genes analysis, to verify the biological effectiveness of our model.

Numerous studies have shown that microRNAs are associated with the occurrence and development of human diseases. Thus, studying disease-associated miRNAs is significantly valuable to the prevention, diagnosis and treatment of diseases. In this paper, we proposed a novel method based on matrix completion and non-negative matrix factorization (MCNMF)for predicting disease-associated miRNAs. Due to the information inadequacy on miRNA similarities and disease similarities, we calculated the latter via two models, and introduced the Gaussian interaction profile kernel similarity. In addition, the matrix completion (MC)was employed to further replenish the miRNA and disease similarities to improve the prediction performance. And to reduce the sparsity of miRNA-disease association matrix, the method of weighted K nearest neighbor (WKNKN)was used, which is a pre-processing step. We also utilized non-negative matrix factorization (NMF)using dual${{\boldsymbol{L}}_{2,1}}$-norm, graph Laplacian regularization, and Tikhonov regularization to effectively avoid the overfitting during the prediction. Finally, several experiments and a case study were implemented to evaluate the effectiveness and performance of the proposed MCNMF model. The results indicated that our method could reliably and effectively predict disease-associated miRNAs.

MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical role in many biological processes, such as cell growth, development, differentiation and aging. Increasing studies have revealed that miRNAs are closely involved in many human diseases. Therefore, the prediction of miRNA-disease associations is of great significance to the study of the pathogenesis, diagnosis and intervention of human disease. However, biological experimentally methods are usually expensive in time and money, while computational methods can provide an efficient way to infer the underlying disease-related miRNAs. In this study, we propose a novel method to predict potential miRNA-disease associations, called SVAEMDA. Our method mainly consider the miRNA-disease association prediction as semi-supervised learning problem. SVAEMDA integrates disease semantic similarity, miRNA functional similarity and respective Gaussian interaction profile (GIP) similarities. The integrated similarities are used to learn the representations of diseases and miRNAs. SVAEMDA trains a variational autoencoder based predictor by using known miRNA-disease associations, with the form of concatenated dense vectors. Reconstruction probability of the predictor is used to measure the correlation of the miRNA-disease pairs. Experimental results show that SVAEMDA outperforms other stat-of-the-art methods. AUC values of SVAEMDA of global leave-one-out cross validation (LOOCV) and 5-fold cross validation (5-fold CV) are 0.9464 and 0.9428 respectively. In addition, case studies of three common human diseases indicate that SVAEMDA obtains 100 percent of the top 50 predicted candidates in the benchmark databases. Therefore, SVAEMDA can efficiently and accurately predict the potential associations between diseases and miRNAs.

Recently, as a growing number of associations between microRNAs (miRNAs) and diseases are discovered, researchers gradually realize that miRNAs are closely related to several complicated biological processes and human diseases. Hence, it is especially important to construct availably models to infer associations between miRNAs and diseases. In this study, we presented Improved Graph Regression for miRNA-Disease Association Prediction (IGRMDA) to observe potential relationship between miRNAs and diseases. In order to reduce the inherent noise existing in the acquired biological datasets, we utilized matrix decomposition algorithm to process miRNA functional similarity and disease semantic similarity and then combining them with existing similarity information to obtain final miRNA similarity data and disease similarity data. Then, we applied miRNA-disease association data, miRNA similarity data and disease similarity data to form corresponding latent spaces. Furthermore, we performed improved graph regression algorithm in latent spaces, which included miRNA-disease association space, miRNA similarity space and disease similarity space. Non-negative matrix factorization and partial least squares were used in the graph regression process to obtain important related attributes. The cross validation experiments and case studies were also implemented to prove the effectiveness of IGRMDA, which showed that IGRMDA could predict potential associations between miRNAs and diseases.

Lots of experimental studies have revealed the significant associations between lncRNAs and diseases. Identifying accurate associations will provide a new perspective for disease therapy. Calculation-based methods have been developed to solve these problems, but these methods have some limitations. In this paper, we proposed an accurate method, named MLGCNET, to discover potential lncRNA-disease associations. Firstly, we reconstructed similarity networks for both lncRNAs and diseases using top k similar information, and constructed a lncRNA-disease heterogeneous network (LDN). Then, we applied Multi-Layer Graph Convolutional Network on LDN to obtain latent feature representations of nodes. Finally, the Extra Trees was used to calculate the probability of association between disease and lncRNA. The results of extensive 5-fold cross-validation experiments show that MLGCNET has superior prediction performance compared to the state-of-the-art methods. Case studies confirm the performance of our model on specific diseases. All the experiment results prove the effectiveness and practicality of MLGCNET in predicting potential lncRNA-disease associations.

Predicting disease-related long non-coding RNAs (lncRNAs) is beneficial to finding of new biomarkers for prevention, diagnosis and treatment of complex human diseases. In this paper, we proposed a machine learning techniques-based classification approach to identify disease-related lncRNAs by graph auto-encoder (GAE) and random forest (RF) (GAERF). First, we combined the relationship of lncRNA, miRNA and disease into a heterogeneous network. Then, low-dimensional representation vectors of nodes were learned from the network by GAE, which reduce the dimension and heterogeneity of biological data. Taking these feature vectors as input, we trained a RF classifier to predict new lncRNA-disease associations (LDAs). Related experiment results show that the proposed method for the representation of lncRNA-disease characterizes them accurately. GAERF achieves superior performance owing to the ensemble learning method, outperforming other methods significantly. Moreover, case studies further demonstrated that GAERF is an effective method to predict LDAs.

MOTIVATION: MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in various biological processes. Many studies have shown that miRNAs are closely related to the occurrence, development and diagnosis of human diseases. Traditional biological experiments are costly and time consuming. As a result, effective computational models have become increasingly popular for predicting associations between miRNAs and diseases, which could effectively boost human disease diagnosis and prevention. RESULTS: We propose a novel computational framework, called AEMDA, to identify associations between miRNAs and diseases. AEMDA applies a learning-based method to extract dense and high-dimensional representations of diseases and miRNAs from integrated disease semantic similarity, miRNA functional similarity and heterogeneous related interaction data. In addition, AEMDA adopts a deep autoencoder that does not need negative samples to retrieve the underlying associations between miRNAs and diseases. Furthermore, the reconstruction error is used as a measurement to predict disease-associated miRNAs. Our experimental results indicate that AEMDA can effectively predict disease-related miRNAs and outperforms state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/CunmeiJi/AEMDA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.

microRNAs (miRNAs) are small non-coding RNAs related to a number of complicated biological processes. A growing body of studies have suggested that miRNAs are closely associated with many human diseases. It is meaningful to consider disease-related miRNAs as potential biomarkers, which could greatly contribute to understanding the mechanisms of complex diseases and benefit the prevention, detection, diagnosis and treatment of extraordinary diseases. In this study, we presented a novel model named Graph Convolutional Autoencoder for miRNA-Disease Association Prediction (GCAEMDA). In the proposed model, we utilized miRNA-miRNA similarities, disease-disease similarities and verified miRNA-disease associations to construct a heterogeneous network, which is applied to learn the embeddings of miRNAs and diseases. In addition, we separately constructed miRNA-based and disease-based sub-networks. Combining the embeddings of miRNAs and diseases, graph convolutional autoencoder (GCAE) was utilized to calculate association scores of miRNA-disease on two sub-networks, respectively. Furthermore, we obtained final prediction scores between miRNAs and diseases by adopting an average ensemble way to integrate the prediction scores from two types of subnetworks. To indicate the accuracy of GCAEMDA, we applied different cross validation methods to evaluate our model whose performances were better than the state-of-the-art models. Case studies on a common human diseases were also implemented to prove the effectiveness of GCAEMDA. The results demonstrated that GCAEMDA was beneficial to infer potential associations of miRNA-disease.

Abstract Background The aberrant expression of microRNAs is closely connected to the occurrence and development of a great deal of human diseases. To study human diseases, numerous effective computational models that are valuable and meaningful have been presented by researchers. Results Here, we present a computational framework based on graph Laplacian regularizedL2,1-nonnegative matrix factorization (GRL2,1-NMF) for inferring possible human disease-connected miRNAs. First, manually validated disease-connected microRNAs were integrated, and microRNA functional similarity information along with two kinds of disease semantic similarities were calculated. Next, we measured Gaussian interaction profile (GIP) kernel similarities for both diseases and microRNAs. Then, we adopted a preprocessing step, namely, weighted K nearest known neighbours (WKNKN), to decrease the sparsity of the miRNA-disease association matrix network. Finally, theGRL2,1-NMF framework was used to predict links between microRNAs and diseases. Conclusions The new method (GRL2, 1-NMF) achieved AUC values of 0.9280 and 0.9276 in global leave-one-out cross validation (global LOOCV) and five-fold cross validation (5-CV), respectively, showing that GRL2, 1-NMF can powerfully discover potential disease-related miRNAs, even if there is no known associated disease.

As conventional intrusion detection systems cannot evolve with ceaselessly changing environment of computational Grid, a model of intrusion detection system named GIDIA based on immunity and multi Agents is developed with hierarchical architecture. Following definitions of immune model, detecting Agent, decision-making Agent, preventing Agent, and controlling Agent, relevant abstract mathematical models, evolving trends and inferential equations of Agents that are used in intrusion detection module, decision-making module, response module, and vaccine formation and distribution module are founded respectively. Theoretical analysis and experimental results show that GIDIA possesses better self-adaptability, higher detection rate, and offers a novel way to secure Grid member sites in the same trust community or different ones cooperatively.