Prediction of disease-related miRNAs by voting with multiple classifiers.

There is strong evidence to support that mutations and dysregulation of miRNAs are associated with a variety of diseases, including cancer. However, the experimental methods used to identify disease-related miRNAs are expensive and time-consuming. Effective computational approaches to identify disease-related miRNAs are in high demand and would aid in the detection of lncRNA biomarkers for disease diagnosis, treatment, and prevention. In this study, we develop an ensemble learning framework to reveal the potential associations between miRNAs and diseases (ELMDA). The ELMDA framework does not rely on the known associations when calculating miRNA and disease similarities and uses multi-classifiers voting to predict disease-related miRNAs. As a result, the average AUC of the ELMDA framework was 0.9229 for the HMDD v2.0 database in a fivefold cross-validation. All potential associations in the HMDD V2.0 database were predicted, and 90% of the top 50 results were verified with the updated HMDD V3.2 database. The ELMDA framework was implemented to investigate gastric neoplasms, prostate neoplasms and colon neoplasms, and 100%, 94%, and 90%, respectively, of the top 50 potential miRNAs were validated by the HMDD V3.2 database. Moreover, the ELMDA framework can predict isolated disease-related miRNAs. In conclusion, ELMDA appears to be a reliable method to uncover disease-associated miRNAs.

Integration of single sample and population analysis for understanding immune evasion mechanisms of lung cancer.

A deep understanding of the complex interaction mechanism between the various cellular components in tumor microenvironment (TME) of lung adenocarcinoma (LUAD) is a prerequisite for understanding its drug resistance, recurrence, and metastasis. In this study, we proposed two complementary computational frameworks for integrating multi-source and multi-omics data, namely ImmuCycReg framework (single sample level) and L0Reg framework (population or subtype level), to carry out difference analysis between the normal population and different LUAD subtypes. Then, we aimed to identify the possible immune escape pathways adopted by patients with different LUAD subtypes, resulting in immune deficiency which may occur at different stages of the immune cycle. More importantly, combining the research results of the single sample level and population level can improve the credibility of the regulatory network analysis results. In addition, we also established a prognostic scoring model based on the risk factors identified by Lasso-Cox method to predict survival of LUAD patients. The experimental results showed that our frameworks could reliably identify transcription factor (TF) regulating immune-related genes and could analyze the dominant immune escape pathways adopted by each LUAD subtype or even a single sample. Note that the proposed computational framework may be also applicable to the immune escape mechanism analysis of pan-cancer.

MAGCNSE: predicting lncRNA-disease associations using multi-view attention graph convolutional network and stacking ensemble model.

BACKGROUND: Many long non-coding RNAs (lncRNAs) have key roles in different human biologic processes and are closely linked to numerous human diseases, according to cumulative evidence. Predicting potential lncRNA-disease associations can help to detect disease biomarkers and perform disease analysis and prevention. Establishing effective computational methods for lncRNA-disease association prediction is critical. RESULTS: In this paper, we propose a novel model named MAGCNSE to predict underlying lncRNA-disease associations. We first obtain multiple feature matrices from the multi-view similarity graphs of lncRNAs and diseases utilizing graph convolutional network. Then, the weights are adaptively assigned to different feature matrices of lncRNAs and diseases using the attention mechanism. Next, the final representations of lncRNAs and diseases is acquired by further extracting features from the multi-channel feature matrices of lncRNAs and diseases using convolutional neural network. Finally, we employ a stacking ensemble classifier, consisting of multiple traditional machine learning classifiers, to make the final prediction. The results of ablation studies in both representation learning methods and classification methods demonstrate the validity of each module. Furthermore, we compare the overall performance of MAGCNSE with that of six other state-of-the-art models, the results show that it outperforms the other methods. Moreover, we verify the effectiveness of using multi-view data of lncRNAs and diseases. Case studies further reveal the outstanding ability of MAGCNSE in the identification of potential lncRNA-disease associations. CONCLUSIONS: The experimental results indicate that MAGCNSE is a useful approach for predicting potential lncRNA-disease associations.

FCMDAP: using miRNA family and cluster information to improve the prediction accuracy of disease related miRNAs.

BACKGROUND: Biological experiments have confirmed the association between miRNAs and various diseases. However, such experiments are costly and time consuming. Computational methods help select potential disease-related miRNAs to improve the efficiency of biological experiments. METHODS: In this work, we develop a novel method using multiple types of data to calculate miRNA and disease similarity based on mutual information, and add miRNA family and cluster information to predict human disease-related miRNAs (FCMDAP). This method not only depends on known miRNA-diseases associations but also accurately measures miRNA and disease similarity and resolves the problem of overestimation. FCMDAP uses the k most similar neighbor recommendation algorithm to predict the association score between miRNA and disease. Information about miRNA cluster is also used to improve prediction accuracy. RESULT: FCMDAP achieves an average AUC of 0.9165 based on leave-one-out cross validation. Results confirm the 100, 98 and 96% of the top 50 predicted miRNAs reported in case studies on colorectal, lung, and pancreatic neoplasms. FCMDAP also exhibits satisfactory performance in predicting diseases without any related miRNAs and miRNAs without any related diseases. CONCLUSIONS: In this study, we present a computational method FCMDAP to improve the prediction accuracy of disease related miRNAs. FCMDAP could be an effective tool for further biological experiments.

BPLLDA: Predicting lncRNA-Disease Associations Based on Simple Paths With Limited Lengths in a Heterogeneous Network.

In recent years, it has been increasingly clear that long noncoding RNAs (lncRNAs) play critical roles in many biological processes associated with human diseases. Inferring potential lncRNA-disease associations is essential to reveal the secrets behind diseases, develop novel drugs, and optimize personalized treatments. However, biological experiments to validate lncRNA-disease associations are very time-consuming and costly. Thus, it is critical to develop effective computational models. In this study, we have proposed a method called BPLLDA to predict lncRNA-disease associations based on paths of fixed lengths in a heterogeneous lncRNA-disease association network. Specifically, BPLLDA first constructs a heterogeneous lncRNA-disease network by integrating the lncRNA-disease association network, the lncRNA functional similarity network, and the disease semantic similarity network. It then infers the probability of an lncRNA-disease association based on paths connecting them and their lengths in the network. Compared to existing methods, BPLLDA has a few advantages, including not demanding negative samples and the ability to predict associations related to novel lncRNAs or novel diseases. BPLLDA was applied to a canonical lncRNA-disease association database called LncRNADisease, together with two popular methods LRLSLDA and GrwLDA. The leave-one-out cross-validation areas under the receiver operating characteristic curve of BPLLDA are 0.87117, 0.82403, and 0.78528, respectively, for predicting overall associations, associations related to novel lncRNAs, and associations related to novel diseases, higher than those of the two compared methods. In addition, cervical cancer, glioma, and non-small-cell lung cancer were selected as case studies, for which the predicted top five lncRNA-disease associations were verified by recently published literature. In summary, BPLLDA exhibits good performances in predicting novel lncRNA-disease associations and associations related to novel lncRNAs and diseases. It may contribute to the understanding of lncRNA-associated diseases like certain cancers.

SRMDAP: SimRank and Density-Based Clustering Recommender Model for miRNA-Disease Association Prediction.

Aberrant expression of microRNAs (miRNAs) can be applied for the diagnosis, prognosis, and treatment of human diseases. Identifying the relationship between miRNA and human disease is important to further investigate the pathogenesis of human diseases. However, experimental identification of the associations between diseases and miRNAs is time-consuming and expensive. Computational methods are efficient approaches to determine the potential associations between diseases and miRNAs. This paper presents a new computational method based on the SimRank and density-based clustering recommender model for miRNA-disease associations prediction (SRMDAP). The AUC of 0.8838 based on leave-one-out cross-validation and case studies suggested the excellent performance of the SRMDAP in predicting miRNA-disease associations. SRMDAP could also predict diseases without any related miRNAs and miRNAs without any related diseases.

Global network random walk for predicting potential human lncRNA-disease associations.

There is more and more evidence that the mutation and dysregulation of long non-coding RNA (lncRNA) are associated with numerous diseases, including cancers. However, experimental methods to identify associations between lncRNAs and diseases are expensive and time-consuming. Effective computational approaches to identify disease-related lncRNAs are in high demand; and would benefit the detection of lncRNA biomarkers for disease diagnosis, treatment, and prevention. In light of some limitations of existing computational methods, we developed a global network random walk model for predicting lncRNA-disease associations (GrwLDA) to reveal the potential associations between lncRNAs and diseases. GrwLDA is a universal network-based method and does not require negative samples. This method can be applied to a disease with no known associated lncRNA (isolated disease) and to lncRNA with no known associated disease (novel lncRNA). The leave-one-out cross validation (LOOCV) method was implemented to evaluate the predicted performance of GrwLDA. As a result, GrwLDA obtained reliable AUCs of 0.9449, 0.8562, and 0.8374 for overall, novel lncRNA and isolated disease prediction, respectively, significantly outperforming previous methods. Case studies of colon, gastric, and kidney cancers were also implemented, and the top 5 disease-lncRNA associations were reported for each disease. Interestingly, 13 (out of the 15) associations were confirmed by literature mining.

Maxdenominator Reweighted Sparse Representation for Tumor Classification.

The classification of tumors is crucial for the proper treatment of cancer. Sparse representation-based classifier (SRC) exhibits good classification performance and has been successfully used to classify tumors using gene expression profile data. In this study, we propose a three-step maxdenominator reweighted sparse representation classification (MRSRC) method to classify tumors. First, we extract a set of metagenes from the training samples. These metagenes can capture the structures inherent to the data and are more effective for classification than the original gene expression data. Second, we use a reweighted regularization method to obtain the sparse representation coefficients. Reweighted regularization can enhance sparsity and obtain better sparse representation coefficients. Third, we classify the data by utilizing a maxdenominator residual error function. Maxdenominator strategy can reduce the residual error and improve the accuracy of the final classification. Extensive experiments using publicly available gene expression profile data sets show that the performance of MRSRC is comparable with or better than many existing representative methods.

Uncover miRNA-Disease Association by Exploiting Global Network Similarity.

Identification of miRNA-disease association is a fundamental challenge in human health clinic. However, the known miRNA-disease associations are rare and experimental verification methods are expensive and time-consuming. Therefore, there is a strong incentive to develop computational methods. In this paper, we calculate the similarity score for each miRNAs pair by integrating miRNA functional similarity and miRNA family information. We use the disease phenotype similarity data to construct the disease similarity network. Then we introduce a new miRNA-disease association prediction method (NETwork Group Similarity, NetGS) to explore the global network similarity, capturing the relationship between the disease and other diseases, the similarity between the potential disease-related miRNA and other miRNAs. Finally based on the consistency of diffusion profiles we get the miRNA-disease association scores. NetGS is tested by the leave-one-out cross validation and achieves an AUC value of 0.8450, which improves the prediction accuracy. NetGS can also be applied to solve the new miRNA-disease association and obtain reliable accuracy. Moreover, we use NetGS to predict new causing miRNAs of three cancers including breast cancer, lung cancer and Hepatocellular cancer. And the top predictions have been confirmed in the online databases. The encouraging results indicate that NetGS might play an essential role for future scientific research.

Network Consistency Projection for Human miRNA-Disease Associations Inference.

Prediction and confirmation of the presence of disease-related miRNAs is beneficial to understand disease mechanisms at the miRNA level. However, the use of experimental verification to identify disease-related miRNAs is expensive and time-consuming. Effective computational approaches used to predict miRNA-disease associations are highly specific. In this study, we develop the Network Consistency Projection for miRNA-Disease Associations (NCPMDA) method to reveal the potential associations between miRNAs and diseases. NCPMDA is a non-parametric universal network-based method that can simultaneously predict miRNA-disease associations in all diseases but does not require negative samples. NCPMDA can also confirm the presence of miRNAs in isolated diseases (diseases without any known miRNA association). Leave-one-out cross validation and case studies have shown that the predictive performance of NCPMDA is superior over that of previous method.