CMFHMDA: a prediction framework for human disease-microbe associations based on cross-domain matrix factorization.

Predicting associations between microbes and diseases opens up new avenues for developing diagnostic, preventive, and therapeutic strategies. Given that laboratory-based biological tests to verify these associations are often time-consuming and expensive, there is a critical need for innovative computational frameworks to predict new microbe-disease associations. In this work, we introduce a novel prediction algorithm called Predicting Human Disease-Microbe Associations using Cross-Domain Matrix Factorization (CMFHMDA). Initially, we calculate the composite similarity of diseases and the Gaussian interaction profile similarity of microbes. We then apply the Weighted K Nearest Known Neighbors (WKNKN) algorithm to refine the microbe-disease association matrix. Our CMFHMDA model is subsequently developed by integrating the network data of both microbes and diseases to predict potential associations. The key innovations of this method include using the WKNKN algorithm to preprocess missing values in the association matrix and incorporating cross-domain information from microbes and diseases into the CMFHMDA model. To validate CMFHMDA, we employed three different cross-validation techniques to evaluate the model's accuracy. The results indicate that the CMFHMDA model achieved Area Under the Receiver Operating Characteristic Curve scores of 0.9172, 0.8551, and 0.9351$\pm $0.0052 in global Leave-One-Out Cross-Validation (LOOCV), local LOOCV, and five-fold CV, respectively. Furthermore, many predicted associations have been confirmed by published experimental studies, establishing CMFHMDA as an effective tool for predicting potential disease-associated microbes.

Dual-channel hypergraph convolutional network for predicting herb-disease associations.

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.

Incorporating higher order network structures to improve miRNA-disease association prediction based on functional modularity.

As microRNAs (miRNAs) are involved in many essential biological processes, their abnormal expressions can serve as biomarkers and prognostic indicators to prevent the development of complex diseases, thus providing accurate early detection and prognostic evaluation. Although a number of computational methods have been proposed to predict miRNA-disease associations (MDAs) for further experimental verification, their performance is limited primarily by the inadequacy of exploiting lower order patterns characterizing known MDAs to identify missing ones from MDA networks. Hence, in this work, we present a novel prediction model, namely HiSCMDA, by incorporating higher order network structures for improved performance of MDA prediction. To this end, HiSCMDA first integrates miRNA similarity network, disease similarity network and MDA network to preserve the advantages of all these networks. After that, it identifies overlapping functional modules from the integrated network by predefining several higher order connectivity patterns of interest. Last, a path-based scoring function is designed to infer potential MDAs based on network paths across related functional modules. HiSCMDA yields the best performance across all datasets and evaluation metrics in the cross-validation and independent validation experiments. Furthermore, in the case studies, 49 and 50 out of the top 50 miRNAs, respectively, predicted for colon neoplasms and lung neoplasms have been validated by well-established databases. Experimental results show that rich higher order organizational structures exposed in the MDA network gain new insight into the MDA prediction based on higher order connectivity patterns.

MPCLCDA: predicting circRNA-disease associations by using automatically selected meta-path and contrastive learning.

Circular RNA (circRNA) is closely associated with human diseases. Accordingly, identifying the associations between human diseases and circRNA can help in disease prevention, diagnosis and treatment. Traditional methods are time consuming and laborious. Meanwhile, computational models can effectively predict potential circRNA-disease associations (CDAs), but are restricted by limited data, resulting in data with high dimension and imbalance. In this study, we propose a model based on automatically selected meta-path and contrastive learning, called the MPCLCDA model. First, the model constructs a new heterogeneous network based on circRNA similarity, disease similarity and known association, via automatically selected meta-path and obtains the low-dimensional fusion features of nodes via graph convolutional networks. Then, contrastive learning is used to optimize the fusion features further, and obtain the node features that make the distinction between positive and negative samples more evident. Finally, circRNA-disease scores are predicted through a multilayer perceptron. The proposed method is compared with advanced methods on four datasets. The average area under the receiver operating characteristic curve, area under the precision-recall curve and F1 score under 5-fold cross-validation reached 0.9752, 0.9831 and 0.9745, respectively. Simultaneously, case studies on human diseases further prove the predictive ability and application value of this method.

End-to-end interpretable disease-gene association prediction.

Identifying disease-gene associations is a fundamental and critical biomedical task towards understanding molecular mechanisms, the diagnosis and treatment of diseases. It is time-consuming and expensive to experimentally verify causal links between diseases and genes. Recently, deep learning methods have achieved tremendous success in identifying candidate genes for genetic diseases. The gene prediction problem can be modeled as a link prediction problem based on the features of nodes and edges of the gene-disease graph. However, most existing researches either build homogeneous networks based on one single data source or heterogeneous networks based on multi-source data, and artificially define meta-paths, so as to learn the network representation of diseases and genes. The former cannot make use of abundant multi-source heterogeneous information, while the latter needs domain knowledge and experience when defining meta-paths, and the accuracy of the model largely depends on the definition of meta-paths. To address the aforementioned challenges above bottlenecks, we propose an end-to-end disease-gene association prediction model with parallel graph transformer network (DGP-PGTN), which deeply integrates the heterogeneous information of diseases, genes, ontologies and phenotypes. DGP-PGTN can automatically and comprehensively capture the multiple latent interactions between diseases and genes, discover the causal relationship between them and is fully interpretable at the same time. We conduct comprehensive experiments and show that DGP-PGTN outperforms the state-of-the-art methods significantly on the task of disease-gene association prediction. Furthermore, DGP-PGTN can automatically learn the implicit relationship between diseases and genes without manually defining meta paths.

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 microbe-drug associations with structure-enhanced contrastive learning and self-paced negative sampling strategy.

MOTIVATION: Predicting the associations between human microbes and drugs (MDAs) is one critical step in drug development and precision medicine areas. Since discovering these associations through wet experiments is time-consuming and labor-intensive, computational methods have already been an effective way to tackle this problem. Recently, graph contrastive learning (GCL) approaches have shown great advantages in learning the embeddings of nodes from heterogeneous biological graphs (HBGs). However, most GCL-based approaches don't fully capture the rich structure information in HBGs. Besides, fewer MDA prediction methods could screen out the most informative negative samples for effectively training the classifier. Therefore, it still needs to improve the accuracy of MDA predictions. RESULTS: In this study, we propose a novel approach that employs the Structure-enhanced Contrastive learning and Self-paced negative sampling strategy for Microbe-Drug Association predictions (SCSMDA). Firstly, SCSMDA constructs the similarity networks of microbes and drugs, as well as their different meta-path-induced networks. Then SCSMDA employs the representations of microbes and drugs learned from meta-path-induced networks to enhance their embeddings learned from the similarity networks by the contrastive learning strategy. After that, we adopt the self-paced negative sampling strategy to select the most informative negative samples to train the MLP classifier. Lastly, SCSMDA predicts the potential microbe-drug associations with the trained MLP classifier. The embeddings of microbes and drugs learning from the similarity networks are enhanced with the contrastive learning strategy, which could obtain their discriminative representations. Extensive results on three public datasets indicate that SCSMDA significantly outperforms other baseline methods on the MDA prediction task. Case studies for two common drugs could further demonstrate the effectiveness of SCSMDA in finding novel MDA associations. AVAILABILITY: The source code is publicly available on GitHub https://github.com/Yue-Yuu/SCSMDA-master.

Matrix reconstruction with reliable neighbors for predicting potential MiRNA-disease associations.

Numerous experimental studies have indicated that alteration and dysregulation in mircroRNAs (miRNAs) are associated with serious diseases. Identifying disease-related miRNAs is therefore an essential and challenging task in bioinformatics research. Computational methods are an efficient and economical alternative to conventional biomedical studies and can reveal underlying miRNA-disease associations for subsequent experimental confirmation with reasonable confidence. Despite the success of existing computational approaches, most of them only rely on the known miRNA-disease associations to predict associations without adding other data to increase the prediction accuracy, and they are affected by issues of data sparsity. In this paper, we present MRRN, a model that combines matrix reconstruction with node reliability to predict probable miRNA-disease associations. In MRRN, the most reliable neighbors of miRNA and disease are used to update the original miRNA-disease association matrix, which significantly reduces data sparsity. Unknown miRNA-disease associations are reconstructed by aggregating the most reliable first-order neighbors to increase prediction accuracy by representing the local and global structure of the heterogeneous network. Five-fold cross-validation of MRRN produced an area under the curve (AUC) of 0.9355 and area under the precision-recall curve (AUPR) of 0.2646, values that were greater than those produced by comparable models. Two different types of case studies using three diseases were conducted to demonstrate the accuracy of MRRN, and all top 30 predicted miRNAs were verified.

CapsNet-LDA: predicting lncRNA-disease associations using attention mechanism and capsule network based on multi-view data.

Cumulative studies have shown that many long non-coding RNAs (lncRNAs) are crucial in a number of diseases. Predicting potential lncRNA-disease associations (LDAs) can facilitate disease prevention, diagnosis and treatment. Therefore, it is vital to develop practical computational methods for LDA prediction. In this study, we propose a novel predictor named capsule network (CapsNet)-LDA for LDA prediction. CapsNet-LDA first uses a stacked autoencoder for acquiring the informative low-dimensional representations of the lncRNA-disease pairs under multiple views, then the attention mechanism is leveraged to implement an adaptive allocation of importance weights to them, and they are subsequently processed using a CapsNet-based architecture for predicting LDAs. Different from the conventional convolutional neural networks (CNNs) that have some restrictions with the usage of scalar neurons and pooling operations. the CapsNets use vector neurons instead of scalar neurons that have better robustness for the complex combination of features and they use dynamic routing processes for updating parameters. CapsNet-LDA is superior to other five state-of-the-art models on four benchmark datasets, four perturbed datasets and an independent test set in the comparison experiments, demonstrating that CapsNet-LDA has excellent performance and robustness against perturbation, as well as good generalization ability. The ablation studies verify the effectiveness of some modules of CapsNet-LDA. Moreover, the ability of multi-view data to improve performance is proven. Case studies further indicate that CapsNet-LDA can accurately predict novel LDAs for specific diseases.

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.

MHCLMDA: multihypergraph contrastive learning for miRNA-disease association prediction.

The correct prediction of disease-associated miRNAs plays an essential role in disease prevention and treatment. Current computational methods to predict disease-associated miRNAs construct different miRNA views and disease views based on various miRNA properties and disease properties and then integrate the multiviews to predict the relationship between miRNAs and diseases. However, most existing methods ignore the information interaction among the views and the consistency of miRNA features (disease features) across multiple views. This study proposes a computational method based on multiple hypergraph contrastive learning (MHCLMDA) to predict miRNA-disease associations. MHCLMDA first constructs multiple miRNA hypergraphs and disease hypergraphs based on various miRNA similarities and disease similarities and performs hypergraph convolution on each hypergraph to capture higher order interactions between nodes, followed by hypergraph contrastive learning to learn the consistent miRNA feature representation and disease feature representation under different views. Then, a variational auto-encoder is employed to extract the miRNA and disease features in known miRNA-disease association relationships. Finally, MHCLMDA fuses the miRNA and disease features from different views to predict miRNA-disease associations. The parameters of the model are optimized in an end-to-end way. We applied MHCLMDA to the prediction of human miRNA-disease association. The experimental results show that our method performs better than several other state-of-the-art methods in terms of the area under the receiver operating characteristic curve and the area under the precision-recall curve.

RSANMDA: Resampling based subview attention network for miRNA-disease association prediction.

Many studies have demonstrated the importance of accurately identifying miRNA-disease associations (MDAs) for understanding disease mechanisms. However, the number of known MDAs is significantly fewer than the unknown pairs. Here, we propose RSANMDA, a subview attention network for predicting MDAs. We first extract miRNA and disease features from multiple similarity matrices. Next, using resampling techniques, we generate different subviews from known MDAs. Each subview undergoes multi-head graph attention to capture its features, followed by semantic attention to integrate features across subviews. Finally, combining raw and training features, we use a multilayer scoring perceptron for prediction. In the experimental section, we conducted comparative experiments with other advanced models on both HMDD v2.0 and HMDD v3.2 datasets. We also performed a series of ablation studies and parameter tuning exercises. Comprehensive experiments conclusively demonstrate the superiority of our model. Case studies on lung, breast, and esophageal cancers further validate our method's predictive capability for identifying disease-related miRNAs.

BEROLECMI: a novel prediction method to infer circRNA-miRNA interaction from the role definition of molecular attributes and biological networks.

Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

DNI-MDCAP: improvement of causal MiRNA-disease association prediction based on deep network imputation.

BACKGROUND: MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction. RESULTS: We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model. CONCLUSIONS: DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/ .

GCNFORMER: graph convolutional network and transformer for predicting lncRNA-disease associations.

BACKGROUND: A growing body of researches indicate that the disrupted expression of long non-coding RNA (lncRNA) is linked to a range of human disorders. Therefore, the effective prediction of lncRNA-disease association (LDA) can not only suggest solutions to diagnose a condition but also save significant time and labor costs. METHOD: In this work, we proposed a novel LDA predicting algorithm based on graph convolutional network and transformer, named GCNFORMER. Firstly, we integrated the intraclass similarity and interclass connections between miRNAs, lncRNAs and diseases, and built a graph adjacency matrix. Secondly, to completely obtain the features between various nodes, we employed a graph convolutional network for feature extraction. Finally, to obtain the global dependencies between inputs and outputs, we used a transformer encoder with a multiheaded attention mechanism to forecast lncRNA-disease associations. RESULTS: The results of fivefold cross-validation experiment on the public dataset revealed that the AUC and AUPR of GCNFORMER achieved 0.9739 and 0.9812, respectively. We compared GCNFORMER with six advanced LDA prediction models, and the results indicated its superiority over the other six models. Furthermore, GCNFORMER's effectiveness in predicting potential LDAs is underscored by case studies on breast cancer, colon cancer and lung cancer. CONCLUSIONS: The combination of graph convolutional network and transformer can effectively improve the performance of LDA prediction model and promote the in-depth development of this research filed.

SCPLPA: An miRNA-disease association prediction model based on spatial consistency projection and label propagation algorithm.

Identifying the association between miRNA and diseases is helpful for disease prevention, diagnosis and treatment. It is of great significance to use computational methods to predict potential human miRNA disease associations. Considering the shortcomings of existing computational methods, such as low prediction accuracy and weak generalization, we propose a new method called SCPLPA to predict miRNA-disease associations. First, a heterogeneous disease similarity network was constructed using the disease semantic similarity network and the disease Gaussian interaction spectrum kernel similarity network, while a heterogeneous miRNA similarity network was constructed using the miRNA functional similarity network and the miRNA Gaussian interaction spectrum kernel similarity network. Then, the estimated miRNA-disease association scores were evaluated by integrating the outcomes obtained by implementing label propagation algorithms in the heterogeneous disease similarity network and the heterogeneous miRNA similarity network. Finally, the spatial consistency projection algorithm of the network was used to extract miRNA disease association features to predict unverified associations between miRNA and diseases. SCPLPA was compared with four classical methods (MDHGI, NSEMDA, RFMDA and SNMFMDA), and the results of multiple evaluation metrics showed that SCPLPA exhibited the most outstanding predictive performance. Case studies have shown that SCPLPA can effectively identify miRNAs associated with colon neoplasms and kidney neoplasms. In summary, our proposed SCPLPA algorithm is easy to implement and can effectively predict miRNA disease associations, making it a reliable auxiliary tool for biomedical research.

Predicting potential microbe-disease associations based on dual branch graph convolutional network.

Studying the association between microbes and diseases not only aids in the prevention and diagnosis of diseases, but also provides crucial theoretical support for new drug development and personalized treatment. Due to the time-consuming and costly nature of laboratory-based biological tests to confirm the relationship between microbes and diseases, there is an urgent need for innovative computational frameworks to anticipate new associations between microbes and diseases. Here, we propose a novel computational approach based on a dual branch graph convolutional network (GCN) module, abbreviated as DBGCNMDA, for identifying microbe-disease associations. First, DBGCNMDA calculates the similarity matrix of diseases and microbes by integrating functional similarity and Gaussian association spectrum kernel (GAPK) similarity. Then, semantic information from different biological networks is extracted by two GCN modules from different perspectives. Finally, the scores of microbe-disease associations are predicted based on the extracted features. The main innovation of this method lies in the use of two types of information for microbe/disease similarity assessment. Additionally, we extend the disease nodes to address the issue of insufficient features due to low data dimensionality. We optimize the connectivity between the homogeneous entities using random walk with restart (RWR), and then use the optimized similarity matrix as the initial feature matrix. In terms of network understanding, we design a dual branch GCN module, namely GlobalGCN and LocalGCN, to fine-tune node representations by introducing side information, including homologous neighbour nodes. We evaluate the accuracy of the DBGCNMDA model using five-fold cross-validation (5-fold-CV) technique. The results show that the area under the receiver operating characteristic curve (AUC) and area under the precision versus recall curve (AUPR) of the DBGCNMDA model in the 5-fold-CV are 0.9559 and 0.9630, respectively. The results from the case studies using published experimental data confirm a significant number of predicted associations, indicating that DBGCNMDA is an effective tool for predicting potential microbe-disease associations.

Research progress of miRNA-disease association prediction and comparison of related algorithms.

With an in-depth understanding of noncoding ribonucleic acid (RNA), many studies have shown that microRNA (miRNA) plays an important role in human diseases. Because traditional biological experiments are time-consuming and laborious, new calculation methods have recently been developed to predict associations between miRNA and diseases. In this review, we collected various miRNA-disease association prediction models proposed in recent years and used two common data sets to evaluate the performance of the prediction models. First, we systematically summarized the commonly used databases and similarity data for predicting miRNA-disease associations, and then divided the various calculation models into four categories for summary and detailed introduction. In this study, two independent datasets (D5430 and D6088) were compiled to systematically evaluate 11 publicly available prediction tools for miRNA-disease associations. The experimental results indicate that the methods based on information dissemination and the method based on scoring function require shorter running time. The method based on matrix transformation often requires a longer running time, but the overall prediction result is better than the previous two methods. We hope that the summary of work related to miRNA and disease will provide comprehensive knowledge for predicting the relationship between miRNA and disease and contribute to advanced computation tools in the future.

Updated review of advances in microRNAs and complex diseases: towards systematic evaluation of computational models.

Currently, there exist no generally accepted strategies of evaluating computational models for microRNA-disease associations (MDAs). Though K-fold cross validations and case studies seem to be must-have procedures, the value of K, the evaluation metrics, and the choice of query diseases as well as the inclusion of other procedures (such as parameter sensitivity tests, ablation studies and computational cost reports) are all determined on a case-by-case basis and depending on the researchers' choices. In the current review, we include a comprehensive analysis on how 29 state-of-the-art models for predicting MDAs were evaluated. Based on the analytical results, we recommend a feasible evaluation workflow that would suit any future model to facilitate fair and systematic assessment of predictive performance.

Prediction of potential miRNA-disease associations based on stacked autoencoder.

In recent years, increasing biological experiments and scientific studies have demonstrated that microRNA (miRNA) plays an important role in the development of human complex diseases. Therefore, discovering miRNA-disease associations can contribute to accurate diagnosis and effective treatment of diseases. Identifying miRNA-disease associations through computational methods based on biological data has been proven to be low-cost and high-efficiency. In this study, we proposed a computational model named Stacked Autoencoder for potential MiRNA-Disease Association prediction (SAEMDA). In SAEMDA, all the miRNA-disease samples were used to pretrain a Stacked Autoencoder (SAE) in an unsupervised manner. Then, the positive samples and the same number of selected negative samples were utilized to fine-tune SAE in a supervised manner after adding an output layer with softmax classifier to the SAE. SAEMDA can make full use of the feature information of all unlabeled miRNA-disease pairs. Therefore, SAEMDA is suitable for our dataset containing small labeled samples and large unlabeled samples. As a result, SAEMDA achieved AUCs of 0.9210 and 0.8343 in global and local leave-one-out cross validation. Besides, SAEMDA obtained an average AUC and standard deviation of 0.9102 ± /-0.0029 in 100 times of 5-fold cross validation. These results were better than those of previous models. Moreover, we carried out three case studies to further demonstrate the predictive accuracy of SAEMDA. As a result, 82% (breast neoplasms), 100% (lung neoplasms) and 90% (esophageal neoplasms) of the top 50 predicted miRNAs were verified by databases. Thus, SAEMDA could be a useful and reliable model to predict potential miRNA-disease associations.