Multi-Kernel Graph Attention Deep Autoencoder for MiRNA-Disease Association Prediction.

Accumulating evidence indicates that microRNAs (miRNAs) can control and coordinate various biological processes. Consequently, abnormal expressions of miRNAs have been linked to various complex diseases. Recognizable proof of miRNA-disease associations (MDAs) will contribute to the diagnosis and treatment of human diseases. Nevertheless, traditional experimental verification of MDAs is laborious and limited to small-scale. Therefore, it is necessary to develop reliable and effective computational methods to predict novel MDAs. In this work, a multi-kernel graph attention deep autoencoder (MGADAE) method is proposed to predict potential MDAs. In detail, MGADAE first employs the multiple kernel learning (MKL) algorithm to construct an integrated miRNA similarity and disease similarity, providing more biological information for further feature learning. Second, MGADAE combines the known MDAs, disease similarity, and miRNA similarity into a heterogeneous network, then learns the representations of miRNAs and diseases through graph convolution operation. After that, an attention mechanism is introduced into MGADAE to integrate the representations from multiple graph convolutional network (GCN) layers. Lastly, the integrated representations of miRNAs and diseases are input into the bilinear decoder to obtain the final predicted association scores. Corresponding experiments prove that the proposed method outperforms existing advanced approaches in MDA prediction. Furthermore, case studies related to two human cancers provide further confirmation of the reliability of MGADAE in practice.

HTRPCA: Hypergraph Regularized Tensor Robust Principal Component Analysis for Sample Clustering in Tumor Omics Data.

In recent years, clustering analysis of cancer genomics data has gained widespread attention. However, limited by the dimensions of the matrix, the traditional methods cannot fully mine the underlying geometric structure information in the data. Besides, noise and outliers inevitably exist in the data. To solve the above two problems, we come up with a new method which uses tensor to represent cancer omics data and applies hypergraph to save the geometric structure information in original data. This model is called hypergraph regularized tensor robust principal component analysis (HTRPCA). The data processed by HTRPCA becomes two parts, one of which is a low-rank component that contains pure underlying structure information between samples, and the other is some sparse interference points. So we can use the low-rank component for clustering. This model can retain complex geometric information between more sample points due to the addition of the hypergraph regularization. Through clustering, we can demonstrate the effectiveness of HTRPCA, and the experimental results on TCGA datasets demonstrate that HTRPCA precedes other advanced methods. This paper proposes a new method of using tensors to represent cancer omics data and introduces hypergraph items to save the geometric structure information of the original data. At the same time, the model decomposes the original tensor into low-order tensors and sparse tensors. The low-rank tensor was used to cluster cancer samples to verify the effectiveness of the method.

MCCMF: collaborative matrix factorization based on matrix completion for predicting miRNA-disease associations.

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations. RESULTS: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the fivefold cross-validation, with an AUC of 0.9569 (0.0005). CONCLUSIONS: The AUC value of MCCMF is higher than other advanced methods in the fivefold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.

Hyper-Graph Regularized Constrained NMF for Selecting Differentially Expressed Genes and Tumor Classification.

Non-negative Matrix Factorization (NMF) is a dimensionality reduction approach for learning a parts-based and linear representation of non-negative data. It has attracted more attention because of that. In practice, NMF not only neglects the manifold structure of data samples, but also overlooks the priori label information of different classes. In this paper, a novel matrix decomposition method called Hyper-graph regularized Constrained Non-negative Matrix Factorization (HCNMF) is proposed for selecting differentially expressed genes and tumor sample classification. The advantage of hyper-graph learning is to capture local spatial information in high dimensional data. This method incorporates a hyper-graph regularization constraint to consider the higher order data sample relationships. The application of hyper-graph theory can effectively find pathogenic genes in cancer datasets. Besides, the label information is further incorporated in the objective function to improve the discriminative ability of the decomposition matrix. Supervised learning with label information greatly improves the classification effect. We also provide the iterative update rules and convergence proofs for the optimization problems of HCNMF. Experiments under The Cancer Genome Atlas (TCGA) datasets confirm the superiority of HCNMF algorithm compared with other representative algorithms through a set of evaluations.