Prediction of lncRNA-disease associations based on robust multi-label learning

2021 ◽  
Vol 16 ◽  
Author(s):  
Jiaxin Zhang ◽  
Quanmeng Sun ◽  
Cheng Liang

Background: Long non-coding RNAs (lncRNAs) are nonprotein-coding transcripts of more than 200 nucleotides in length. In recent years, studies have shown that long non-coding RNAs (lncRNA) play a vital role in various biological processes, complex disease diagnosis, prognosis, and treatment. Objective: Analysis of known lncRNA-disease associations and the prediction of potential lncRNA-disease associations are necessary to provide the most probable candidates for subsequent experimental validation. Methods: In this paper, we present a novel robust computational framework for lncRNA-disease association prediction by combining the ℓ1-norm graph with multi-label learning. Specifically, we first construct a set of similarity matrices for lncRNAs and diseases using known associations. Then, both lncRNA and disease similarity matrices are adaptively re-weighted to enhance the robustness via the ℓ1-norm graph. Lastly, the association matrix is updated with a graph-based multi-label learning framework to uncover the underlying consistency between the lncRNA space and the disease space. Results : We compared the proposed method with the four latest methods on five widely used data sets. The experimental results show that our method can achieve comparable performance in both five-fold cross-validation and leave-one-disease-out cross-validation prediction tasks. The case study of prostate cancer further confirms the practicability of our approach in identifying lncRNAs as potential prognostic biomarkers. Conclusion: Our method can serve as a useful tool for the prediction of novel lncRNA-disease associations.

2019 ◽  
Vol 21 (4) ◽  
pp. 1356-1367 ◽  
Author(s):  
Hang Wei ◽  
Bin Liu

Abstract Circular RNAs (circRNAs) are a group of novel discovered non-coding RNAs with closed-loop structure, which play critical roles in various biological processes. Identifying associations between circRNAs and diseases is critical for exploring the complex disease mechanism and facilitating disease-targeted therapy. Although several computational predictors have been proposed, their performance is still limited. In this study, a novel computational method called iCircDA-MF is proposed. Because the circRNA-disease associations with experimental validation are very limited, the potential circRNA-disease associations are calculated based on the circRNA similarity and disease similarity extracted from the disease semantic information and the known associations of circRNA-gene, gene-disease and circRNA-disease. The circRNA-disease interaction profiles are then updated by the neighbour interaction profiles so as to correct the false negative associations. Finally, the matrix factorization is performed on the updated circRNA-disease interaction profiles to predict the circRNA-disease associations. The experimental results on a widely used benchmark dataset showed that iCircDA-MF outperforms other state-of-the-art predictors and can identify new circRNA-disease associations effectively.


Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1040 ◽  
Author(s):  
Li Zhang ◽  
Xing Chen ◽  
Jun Yin

The important role of microRNAs (miRNAs) in the formation, development, diagnosis, and treatment of diseases has attracted much attention among researchers recently. In this study, we present an unsupervised deep learning model of the variational autoencoder for MiRNA–disease association prediction (VAEMDA). Through combining the integrated miRNA similarity and the integrated disease similarity with known miRNA–disease associations, respectively, we constructed two spliced matrices. These matrices were applied to train the variational autoencoder (VAE), respectively. The final predicted association scores between miRNAs and diseases were obtained by integrating the scores from the two trained VAE models. Unlike previous models, VAEMDA can avoid noise introduced by the random selection of negative samples and reveal associations between miRNAs and diseases from the perspective of data distribution. Compared with previous methods, VAEMDA obtained higher area under the receiver operating characteristics curves (AUCs) of 0.9118, 0.8652, and 0.9091 ± 0.0065 in global leave-one-out cross validation (LOOCV), local LOOCV, and five-fold cross validation, respectively. Further, the AUCs of VAEMDA were 0.8250 and 0.8237 in global leave-one-disease-out cross validation (LODOCV), and local LODOCV, respectively. In three different types of case studies on three important diseases, the results showed that most of the top 50 potentially associated miRNAs were verified by databases and the literature.


2020 ◽  
Vol 15 ◽  
Author(s):  
Xinguo Lu ◽  
Yan Gao ◽  
Zhenghao Zhu ◽  
Li Ding ◽  
Xinyu Wang ◽  
...  

: MicroRNA is a type of non-coding RNA molecule whose length is about 22 nucleotides. The growing evidence shows that microRNA makes critical regulations in the development of complex diseases, such as cancers, cardiovascular diseases. Predicting potential microRNA-disease associations can provide a new perspective to achieve a better scheme of disease diagnosis and prognosis. However, there is a challenge to predict some potential essential microRNAs only with few known associations. To tackle this, we propose a novel method, named as constrained strategy for predicting microRNA-disease associations called CPMDA, in heterogeneous omics data. Here, we firstly construct disease similarity network and microRNA similarity network to preprocess the microRNAs with none available associations. Then, we apply probabilistic factorization to obtain two feature matrices of microRNA and disease. Meanwhile, we formulate a similarity feature matrix as constraints in the factorization process. Finally, we utilize obtained feature matrixes to identify potential associations for all diseases. The results indicate that CPMDA is superior over other methods in predicting potential microRNA-disease associations. Moreover, the evaluation show that CPMDA has a strong effect on microRNAs with few known associations. In case studies, CPMDA also demonstrated the effectiveness to infer unknown microRNAdisease associations for those novel diseases and microRNAs.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Di Wang ◽  
Yan Cui ◽  
Yuxuan Cao ◽  
Yuehan He ◽  
Hui Chen

Microorganisms in the human body play a vital role in metabolism, immune defense, nutrient absorption, cancer control, and prevention of pathogen colonization. More and more biological and clinical studies have shown that the imbalance of microbial communities is closely related to the occurrence and development of various complex human diseases. Finding potential microbial-disease associations is critical for understanding the pathology of a few diseases and thus further improving disease diagnosis and prognosis. In this study, we proposed a novel computational model to predict disease-associated microbes. Specifically, we first constructed a heterogeneous interconnection network based on known microbe-disease associations deposited in a few databases, the similarity between diseases, and the similarity between microorganisms. We then predicted novel microbe-disease associations by a new method called the double-ended restart random walk model (DRWHMDA) implemented on the interconnection network. In addition, we performed case studies of colon cancer and asthma for further evaluation. The results indicate that 10 and 9 of the top 10 microorganisms predicted to be associated with colorectal cancer and asthma were validated by relevant literatures, respectively. Our method is expected to be effective in identifying disease-related microorganisms and will help to reveal the relationship between microorganisms and complex human diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyu Yang ◽  
Linai Kuang ◽  
Zhiping Chen ◽  
Lei Wang

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe–disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe–disease associations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Tian Wang ◽  
Lei Li ◽  
Cun-Mei Ji ◽  
Chun-Hou Zheng ◽  
Jian-Cheng Ni

MicroRNAs (miRNAs) are small non-coding RNAs that have been demonstrated to be related to numerous complex human diseases. Considerable studies have suggested that miRNAs affect many complicated bioprocesses. Hence, the investigation of disease-related miRNAs by utilizing computational methods is warranted. In this study, we presented an improved label propagation for miRNA–disease association prediction (ILPMDA) method to observe disease-related miRNAs. First, we utilized similarity kernel fusion to integrate different types of biological information for generating miRNA and disease similarity networks. Second, we applied the weighted k-nearest known neighbor algorithm to update verified miRNA–disease association data. Third, we utilized improved label propagation in disease and miRNA similarity networks to make association prediction. Furthermore, we obtained final prediction scores by adopting an average ensemble method to integrate the two kinds of prediction results. To evaluate the prediction performance of ILPMDA, two types of cross-validation methods and case studies on three significant human diseases were implemented to determine the accuracy and effectiveness of ILPMDA. All results demonstrated that ILPMDA had the ability to discover potential miRNA–disease associations.


2021 ◽  
Vol 17 (12) ◽  
pp. e1009655
Author(s):  
Lei Li ◽  
Yu-Tian Wang ◽  
Cun-Mei Ji ◽  
Chun-Hou Zheng ◽  
Jian-Cheng Ni ◽  
...  

microRNAs (miRNAs) are small non-coding RNAs related to a number of complicated biological processes. A growing body of studies have suggested that miRNAs are closely associated with many human diseases. It is meaningful to consider disease-related miRNAs as potential biomarkers, which could greatly contribute to understanding the mechanisms of complex diseases and benefit the prevention, detection, diagnosis and treatment of extraordinary diseases. In this study, we presented a novel model named Graph Convolutional Autoencoder for miRNA-Disease Association Prediction (GCAEMDA). In the proposed model, we utilized miRNA-miRNA similarities, disease-disease similarities and verified miRNA-disease associations to construct a heterogeneous network, which is applied to learn the embeddings of miRNAs and diseases. In addition, we separately constructed miRNA-based and disease-based sub-networks. Combining the embeddings of miRNAs and diseases, graph convolution autoencoder (GCAE) is utilized to calculate association scores of miRNA-disease on two sub-networks, respectively. Furthermore, we obtained final prediction scores between miRNAs and diseases by adopting an average ensemble way to integrate the prediction scores from two types of subnetworks. To indicate the accuracy of GCAEMDA, we applied different cross validation methods to evaluate our model whose performance were better than the state-of-the-art models. Case studies on a common human diseases were also implemented to prove the effectiveness of GCAEMDA. The results demonstrated that GCAEMDA were beneficial to infer potential associations of miRNA-disease.


2015 ◽  
Vol 13 (04) ◽  
pp. 1550014 ◽  
Author(s):  
Bo Liao ◽  
Sumei Ding ◽  
Haowen Chen ◽  
Zejun Li ◽  
Lijun Cai

Identifying the microRNA–disease relationship is vital for investigating the pathogenesis of various diseases. However, experimental verification of disease-related microRNAs remains considerable challenge to many researchers, particularly for the fact that numerous new microRNAs are discovered every year. As such, development of computational methods for disease-related microRNA prediction has recently gained eminent attention. In this paper, first, we construct a miRNA functional network and a disease similarity network by integrating different information sources. Then, we further introduce a new diffusion-based method (NDBM) to explore global network similarity for miRNA–disease association inference. Even though known miRNA–disease associations in the database are rare, NDBM still achieves an area under the ROC curve (AUC) of 85.62% in the leave-one-out cross-validation in improving the prediction accuracy of previous methods significantly. Moreover, our method is applicable to diseases with no known related miRNAs as well as new miRNAs with unknown target diseases. Some associations who strongly predicted by our method are confirmed by public databases. These superior performances suggest that NDBM could be an effective and important tool for biomedical research.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Wang ◽  
Cheng Zhong

The existing studies have shown that miRNAs are related to human diseases by regulating gene expression. Identifying miRNA association with diseases will contribute to diagnosis, treatment, and prognosis of diseases. The experimental identification of miRNA-disease associations is time-consuming, tremendously expensive, and of high-failure rate. In recent years, many researchers predicted potential associations between miRNAs and diseases by computational approaches. In this paper, we proposed a novel method using deep collaborative filtering called DCFMDA to predict miRNA-disease potential associations. To improve prediction performance, we integrated neural network matrix factorization (NNMF) and multilayer perceptron (MLP) in a deep collaborative filtering framework. We utilized known miRNA-disease associations to capture miRNA-disease interaction features by NNMF and utilized miRNA similarity and disease similarity to extract miRNA feature vector and disease feature vector, respectively, by MLP. At last, we merged outputs of the NNMF and MLP to obtain the prediction matrix. The experimental results indicate that compared with other existing computational methods, our method can achieve the AUC of 0.9466 based on 10-fold cross-validation. In addition, case studies show that the DCFMDA can effectively predict candidate miRNAs for breast neoplasms, colon neoplasms, kidney neoplasms, leukemia, and lymphoma.


Author(s):  
Cunmei Ji ◽  
Zhen Gao ◽  
Xu Ma ◽  
Qingwen Wu ◽  
Jiancheng Ni ◽  
...  

Abstract Motivation MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in various biological processes. Many studies have shown that miRNAs are closely related to the occurrence, development and diagnosis of human diseases. Traditional biological experiments are costly and time consuming. As a result, effective computational models have become increasingly popular for predicting associations between miRNAs and diseases, which could effectively boost human disease diagnosis and prevention. Results We propose a novel computational framework, called AEMDA, to identify associations between miRNAs and diseases. AEMDA applies a learning-based method to extract dense and high-dimensional representations of diseases and miRNAs from integrated disease semantic similarity, miRNA functional similarity and heterogeneous related interaction data. In addition, AEMDA adopts a deep autoencoder that does not need negative samples to retrieve the underlying associations between miRNAs and diseases. Furthermore, the reconstruction error is used as a measurement to predict disease-associated miRNAs. Our experimental results indicate that AEMDA can effectively predict disease-related miRNAs and outperforms state-of-the-art methods. Availability and implementation The source code and data are available at https://github.com/CunmeiJi/AEMDA. Supplementary information Supplementary data are available at Bioinformatics online.


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