Identifying potential small molecule-miRNA associations via Robust PCA based on γ-norm regularization.

Dysregulation of microRNAs (miRNAs) is closely associated with refractory human diseases, and the identification of potential associations between small molecule (SM) drugs and miRNAs can provide valuable insights for clinical treatment. Existing computational techniques for inferring potential associations suffer from limitations in terms of accuracy and efficiency. To address these challenges, we devise a novel predictive model called RPCA$\Gamma $NR, in which we propose a new Robust principal component analysis (PCA) framework based on $\gamma $-norm and $l_{2,1}$-norm regularization and design an Augmented Lagrange Multiplier method to optimize it, thereby deriving the association scores. The Gaussian Interaction Profile Kernel Similarity is calculated to capture the similarity information of SMs and miRNAs in known associations. Through extensive evaluation, including Cross Validation Experiments, Independent Validation Experiment, Efficiency Analysis, Ablation Experiment, Matrix Sparsity Analysis, and Case Studies, RPCA$\Gamma $NR outperforms state-of-the-art models concerning accuracy, efficiency and robustness. In conclusion, RPCA$\Gamma $NR can significantly streamline the process of determining SM-miRNA associations, thus contributing to advancements in drug development and disease treatment.

Predicting potential small molecule-miRNA associations utilizing truncated schatten p-norm.

MicroRNAs (miRNAs) have significant implications in diverse human diseases and have proven to be effectively targeted by small molecules (SMs) for therapeutic interventions. However, current SM-miRNA association prediction models do not adequately capture SM/miRNA similarity. Matrix completion is an effective method for association prediction, but existing models use nuclear norm instead of rank function, which has some drawbacks. Therefore, we proposed a new approach for predicting SM-miRNA associations by utilizing the truncated schatten p-norm (TSPN). First, the SM/miRNA similarity was preprocessed by incorporating the Gaussian interaction profile kernel similarity method. This identified more SM/miRNA similarities and significantly improved the SM-miRNA prediction accuracy. Next, we constructed a heterogeneous SM-miRNA network by combining biological information from three matrices and represented the network with its adjacency matrix. Finally, we constructed the prediction model by minimizing the truncated schatten p-norm of this adjacency matrix and we developed an efficient iterative algorithmic framework to solve the model. In this framework, we also used a weighted singular value shrinkage algorithm to avoid the problem of excessive singular value shrinkage. The truncated schatten p-norm approximates the rank function more closely than the nuclear norm, so the predictions are more accurate. We performed four different cross-validation experiments on two separate datasets, and TSPN outperformed various most advanced methods. In addition, public literature confirms a large number of predictive associations of TSPN in four case studies. Therefore, TSPN is a reliable model for SM-miRNA association prediction.

MSGNN-DTA: Multi-Scale Topological Feature Fusion Based on Graph Neural Networks for Drug-Target Binding Affinity Prediction.

The accurate prediction of drug-target binding affinity (DTA) is an essential step in drug discovery and drug repositioning. Although deep learning methods have been widely adopted for DTA prediction, the complexity of extracting drug and target protein features hampers the accuracy of these predictions. In this study, we propose a novel model for DTA prediction named MSGNN-DTA, which leverages a fused multi-scale topological feature approach based on graph neural networks (GNNs). To address the challenge of accurately extracting drug and target protein features, we introduce a gated skip-connection mechanism during the feature learning process to fuse multi-scale topological features, resulting in information-rich representations of drugs and proteins. Our approach constructs drug atom graphs, motif graphs, and weighted protein graphs to fully extract topological information and provide a comprehensive understanding of underlying molecular interactions from multiple perspectives. Experimental results on two benchmark datasets demonstrate that MSGNN-DTA outperforms the state-of-the-art models in all evaluation metrics, showcasing the effectiveness of the proposed approach. Moreover, the study conducts a case study based on already FDA-approved drugs in the DrugBank dataset to highlight the potential of the MSGNN-DTA framework in identifying drug candidates for specific targets, which could accelerate the process of virtual screening and drug repositioning.

Heterogeneous graph inference with range constrainted L2,1-collaborative matrix factorization for small molecule-miRNA association prediction.

MicroRNAs (miRNAs) play a vital role in regulating gene expression and various biological processes. As a result, they have been identified as effective targets for small molecule (SM) drugs in disease treatment. Heterogeneous graph inference stands as a classical approach for predicting SM-miRNA associations, showcasing commendable convergence accuracy and speed. However, most existing methods do not adequately address the inherent sparsity in SM-miRNA association networks, and imprecise SM/miRNA similarity metrics reduce the accuracy of predicting SM-miRNA associations. In this research, we proposed a heterogeneous graph inference with range constrained L2,1-collaborative matrix factorization (HGIRCLMF) method to predict potential SM-miRNA associations. First, we computed the multi-source similarities of SM/miRNA and integrated these similarity information into a comprehensive SM/miRNA similarity. This step improved the accuracy of SM and miRNA similarity, ensuring reliability for the subsequent inference of the heterogeneity map. Second, we used a range constrained L2,1-collaborative matrix factorization (RCLMF) model to pre-populate the SM-miRNA association matrix with missing values. In this step, we developed a novel matrix decomposition method that enhances the robustness and formative nature of SM-miRNA edges between SM networks and miRNA networks. Next, we built a well-established SM-miRNA heterogeneous network utilizing the processed biological information. Finally, HGIRCLMF used this network data to infer unknown association pair scores. We implemented four cross-validation experiments on two distinct datasets, and HGIRCLMF acquired the highest areas under the curve, surpassing six state-of-the-art computational approaches. Furthermore, we performed three case studies to validate the predictive power of our method in practical application.

AMCSMMA: Predicting Small Molecule-miRNA Potential Associations Based on Accurate Matrix Completion.

Exploring potential associations between small molecule drugs (SMs) and microRNAs (miRNAs) is significant for drug development and disease treatment. Since biological experiments are expensive and time-consuming, we propose a computational model based on accurate matrix completion for predicting potential SM-miRNA associations (AMCSMMA). Initially, a heterogeneous SM-miRNA network is constructed, and its adjacency matrix is taken as the target matrix. An optimization framework is then proposed to recover the target matrix with the missing values by minimizing its truncated nuclear norm, an accurate, robust, and efficient approximation to the rank function. Finally, we design an effective two-step iterative algorithm to solve the optimization problem and obtain the prediction scores. After determining the optimal parameters, we conduct four kinds of cross-validation experiments based on two datasets, and the results demonstrate that AMCSMMA is superior to the state-of-the-art methods. In addition, we implement another validation experiment, in which more evaluation metrics in addition to the AUC are introduced and finally achieve great results. In two types of case studies, a large number of SM-miRNA pairs with high predictive scores are confirmed by the published experimental literature. In summary, AMCSMMA has superior performance in predicting potential SM-miRNA associations, which can provide guidance for biological experiments and accelerate the discovery of new SM-miRNA associations.

SGAEMDA: Predicting miRNA-Disease Associations Based on Stacked Graph Autoencoder.

MicroRNA (miRNA)-disease association (MDA) prediction is critical for disease prevention, diagnosis, and treatment. Traditional MDA wet experiments, on the other hand, are inefficient and costly.Therefore, we proposed a multi-layer collaborative unsupervised training base model called SGAEMDA (Stacked Graph Autoencoder-Based Prediction of Potential miRNA-Disease Associations). First, from the original miRNA and disease data, we defined two types of initial features: similarity features and association features. Second, stacked graph autoencoder is then used to learn unsupervised low-dimensional representations of meaningful higher-order similarity features, and we concatenate the association features with the learned low-dimensional representations to obtain the final miRNA-disease pair features. Finally, we used a multilayer perceptron (MLP) to predict scores for unknown miRNA-disease associations. SGAEMDA achieved a mean area under the ROC curve of 0.9585 and 0.9516 in 5-fold and 10-fold cross-validation, which is significantly higher than the other baseline methods. Furthermore, case studies have shown that SGAEMDA can accurately predict candidate miRNAs for brain, breast, colon, and kidney neoplasms.