HTFSMMA: Higher-Order Topological Guided Small Molecule-MicroRNA Associations Prediction.

Small molecules (SMs) play a pivotal role in regulating microRNAs (miRNAs). Existing prediction methods for associations between SM-miRNA have overlooked crucial aspects: the incorporation of local topological features between nodes, which represent either SMs or miRNAs, and the effective fusion of node features with topological features. This study introduces a novel approach, termed high-order topological features for SM-miRNA association prediction (HTFSMMA), which specifically addresses these limitations. Initially, an association graph is formed by integrating SM-miRNA association data, SM similarity, and miRNA similarity. Subsequently, we focus on the local information of links and propose target neighborhood graph convolutional network for extracting local topological features. Then, HTFSMMA employs graph attention networks to amalgamate these local features, thereby establishing a platform for the acquisition of high-order features through random walks. Finally, the extracted features are integrated into the multilayer perceptron to derive the association prediction scores. To demonstrate the performance of HTFSMMA, we conducted comprehensive evaluations including five-fold cross-validation, leave-one-out cross-validation (LOOCV), SM-fixed local LOOCV, and miRNA-fixed local LOOCV. The area under receiver operating characteristic curve values were 0.9958 ± 0.0024 (0.8722 ± 0.0021), 0.9986 (0.9504), 0.9974 (0.9111), and 0.9977 (0.9074), respectively. Our findings demonstrate the superior performance of HTFSMMA over existing approaches. In addition, three case studies and the DeLong test have confirmed the effectiveness of the proposed method. These results collectively underscore the significance of HTFSMMA in facilitating the inference of associations between SMs and miRNAs.

Prediction of MicroRNA-Disease Potential Association Based on Sparse Learning and Multilayer Random Walks.

More and more studies have shown that microRNAs (miRNAs) play an indispensable role in the study of complex diseases in humans. Traditional biological experiments to detect miRNA-disease associations are expensive and time-consuming. Therefore, it is necessary to propose efficient and meaningful computational models to predict miRNA-disease associations. In this study, we aim to propose a miRNA-disease association prediction model based on sparse learning and multilayer random walks (SLMRWMDA). The miRNA-disease association matrix is decomposed and reconstructed by the sparse learning method to obtain richer association information, and at the same time, the initial probability matrix for the random walk with restart algorithm is obtained. The disease similarity network, miRNA similarity network, and miRNA-disease association network are used to construct heterogeneous networks, and the stable probability is obtained based on the topological structure features of diseases and miRNAs through a multilayer random walk algorithm to predict miRNA-disease potential association. The experimental results show that the prediction accuracy of this model is significantly improved compared with the previous related models. We evaluated the model using global leave-one-out cross-validation (global LOOCV) and fivefold cross-validation (5-fold CV). The area under the curve (AUC) value for the LOOCV is 0.9368. The mean AUC value for 5-fold CV is 0.9335 and the variance is 0.0004. In the case study, the results show that SLMRWMDA is effective in inferring the potential association of miRNA-disease.

Prediction of potential drug-microbe associations based on matrix factorization and a three-layer heterogeneous network.

Microbes in the human body are closely linked to many complex human diseases and are emerging as new drug targets. These microbes play a crucial role in drug development and disease treatment. Traditional methods of biological experiments are not only time-consuming but also costly. Using computational methods to predict microbe-drug associations can effectively complement biological experiments. In this experiment, we constructed heterogeneity networks for drugs, microbes, and diseases using multiple biomedical data sources. Then, we developed a model with matrix factorization and a three-layer heterogeneous network (MFTLHNMDA) to predict potential drug-microbe associations. The probability of microbe-drug association was obtained by a global network-based update algorithm. Finally, the performance of MFTLHNMDA was evaluated in the framework of leave-one-out cross-validation (LOOCV) and 5-fold cross-validation (5-fold CV). The results showed that our model performed better than six state-of-the-art methods that had AUC of 0.9396 and 0.9385 + /- 0.0000, respectively. This case study further confirms the effectiveness of MFTLHNMDA in identifying potential drug-microbe associations and new drug-microbe associations.