scholarly journals Improved Prediction of miRNA-Disease Associations Based on Matrix Completion with Network Regularization

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 881 ◽  
Author(s):  
Jihwan Ha ◽  
Chihyun Park ◽  
Chanyoung Park ◽  
Sanghyun Park

The identification of potential microRNA (miRNA)-disease associations enables the elucidation of the pathogenesis of complex human diseases owing to the crucial role of miRNAs in various biologic processes and it yields insights into novel prognostic markers. In the consideration of the time and costs involved in wet experiments, computational models for finding novel miRNA-disease associations would be a great alternative. However, computational models, to date, are biased towards known miRNA-disease associations; this is not suitable for rare miRNAs (i.e., miRNAs with a few known disease associations) and uncommon diseases (i.e., diseases with a few known miRNA associations). This leads to poor prediction accuracies. The most straightforward way of improving the performance is by increasing the number of known miRNA-disease associations. However, due to lack of information, increasing attention has been paid to developing computational models that can handle insufficient data via a technical approach. In this paper, we present a general framework—improved prediction of miRNA-disease associations (IMDN)—based on matrix completion with network regularization to discover potential disease-related miRNAs. The success of adopting matrix factorization is demonstrated by its excellent performance in recommender systems. This approach considers a miRNA network as additional implicit feedback and makes predictions for disease associations relevant to a given miRNA based on its direct neighbors. Our experimental results demonstrate that IMDN achieved excellent performance with reliable area under the receiver operating characteristic (ROC) area under the curve (AUC) values of 0.9162 and 0.8965 in the frameworks of global and local leave-one-out cross-validations (LOOCV), respectively. Further, case studies demonstrated that our method can not only validate true miRNA-disease associations but also suggest novel disease-related miRNA candidates.

2019 ◽  
Vol 35 (22) ◽  
pp. 4730-4738 ◽  
Author(s):  
Yan Zhao ◽  
Xing Chen ◽  
Jun Yin

AbstractMotivationRecent studies have shown that microRNAs (miRNAs) play a critical part in several biological processes and dysregulation of miRNAs is related with numerous complex human diseases. Thus, in-depth research of miRNAs and their association with human diseases can help us to solve many problems.ResultsDue to the high cost of traditional experimental methods, revealing disease-related miRNAs through computational models is a more economical and efficient way. Considering the disadvantages of previous models, in this paper, we developed adaptive boosting for miRNA-disease association prediction (ABMDA) to predict potential associations between diseases and miRNAs. We balanced the positive and negative samples by performing random sampling based on k-means clustering on negative samples, whose process was quick and easy, and our model had higher efficiency and scalability for large datasets than previous methods. As a boosting technology, ABMDA was able to improve the accuracy of given learning algorithm by integrating weak classifiers that could score samples to form a strong classifier based on corresponding weights. Here, we used decision tree as our weak classifier. As a result, the area under the curve (AUC) of global and local leave-one-out cross validation reached 0.9170 and 0.8220, respectively. What is more, the mean and the standard deviation of AUCs achieved 0.9023 and 0.0016, respectively in 5-fold cross validation. Besides, in the case studies of three important human cancers, 49, 50 and 50 out of the top 50 predicted miRNAs for colon neoplasms, hepatocellular carcinoma and breast neoplasms were confirmed by the databases and experimental literatures.Availability and implementationThe code and dataset of ABMDA are freely available at https://github.com/githubcode007/ABMDA.Supplementary informationSupplementary data are available at Bioinformatics online.


2020 ◽  
Vol 21 (4) ◽  
pp. 1508
Author(s):  
Yi Zhang ◽  
Min Chen ◽  
Ang Li ◽  
Xiaohui Cheng ◽  
Hong Jin ◽  
...  

Long non-coding RNAs (long ncRNAs, lncRNAs) of all kinds have been implicated in a range of cell developmental processes and diseases, while they are not translated into proteins. Inferring diseases associated lncRNAs by computational methods can be helpful to understand the pathogenesis of diseases, but those current computational methods still have not achieved remarkable predictive performance: such as the inaccurate construction of similarity networks and inadequate numbers of known lncRNA–disease associations. In this research, we proposed a lncRNA–disease associations inference based on integrated space projection scores (LDAI-ISPS) composed of the following key steps: changing the Boolean network of known lncRNA–disease associations into the weighted networks via combining all the global information (e.g., disease semantic similarities, lncRNA functional similarities, and known lncRNA–disease associations); obtaining the space projection scores via vector projections of the weighted networks to form the final prediction scores without biases. The leave-one-out cross validation (LOOCV) results showed that, compared with other methods, LDAI-ISPS had a higher accuracy with area-under-the-curve (AUC) value of 0.9154 for inferring diseases, with AUC value of 0.8865 for inferring new lncRNAs (whose associations related to diseases are unknown), with AUC value of 0.7518 for inferring isolated diseases (whose associations related to lncRNAs are unknown). A case study also confirmed the predictive performance of LDAI-ISPS as a helper for traditional biological experiments in inferring the potential LncRNA–disease associations and isolated diseases.


Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 126 ◽  
Author(s):  
Zhanwei Xuan ◽  
Jiechen Li ◽  
Jingwen Yu ◽  
Xiang Feng ◽  
Bihai Zhao ◽  
...  

Recently, an increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) can participate in various crucial biological processes and can also be used as the most promising biomarkers for the treatment of certain diseases such as coronary artery disease and various cancers. Due to costs and time complexity, the number of possible disease-related lncRNAs that can be verified by traditional biological experiments is very limited. Therefore, in recent years, it has been very popular to use computational models to predict potential disease-lncRNA associations. In this study, we constructed three kinds of association networks, namely the lncRNA-miRNA association network, the miRNA-disease association network, and the lncRNA-disease correlation network firstly. Then, through integrating these three newly constructed association networks, we constructed an lncRNA-disease weighted association network, which would be further updated by adopting the KNN algorithm based on the semantic similarity of diseases and the similarity of lncRNA functions. Thereafter, according to the updated lncRNA-disease weighted association network, a novel computational model called PMFILDA was proposed to infer potential lncRNA-disease associations based on the probability matrix decomposition. Finally, to evaluate the superiority of the new prediction model PMFILDA, we performed Leave One Out Cross-Validation (LOOCV) based on strongly validated data filtered from MNDR and the simulation results indicated that the performance of PMFILDA was better than some state-of-the-art methods. Moreover, case studies of breast cancer, lung cancer, and colorectal cancer were implemented to further estimate the performance of PMFILDA, and simulation results illustrated that PMFILDA could achieve satisfying prediction performance as well.


2019 ◽  
Vol 20 (7) ◽  
pp. 1549 ◽  
Author(s):  
Yang Liu ◽  
Xiang Feng ◽  
Haochen Zhao ◽  
Zhanwei Xuan ◽  
Lei Wang

Accumulating studies have shown that long non-coding RNAs (lncRNAs) are involved in many biological processes and play important roles in a variety of complex human diseases. Developing effective computational models to identify potential relationships between lncRNAs and diseases can not only help us understand disease mechanisms at the lncRNA molecular level, but also promote the diagnosis, treatment, prognosis, and prevention of human diseases. For this paper, a network-based model called NBLDA was proposed to discover potential lncRNA–disease associations, in which two novel lncRNA–disease weighted networks were constructed. They were first based on known lncRNA–disease associations and topological similarity of the lncRNA–disease association network, and then an lncRNA–lncRNA weighted matrix and a disease–disease weighted matrix were obtained based on a resource allocation strategy of unequal allocation and unbiased consistence. Finally, a label propagation algorithm was applied to predict associated lncRNAs for the investigated diseases. Moreover, in order to estimate the prediction performance of NBLDA, the framework of leave-one-out cross validation (LOOCV) was implemented on NBLDA, and simulation results showed that NBLDA can achieve reliable areas under the ROC curve (AUCs) of 0.8846, 0.8273, and 0.8075 in three known lncRNA–disease association datasets downloaded from the lncRNADisease database, respectively. Furthermore, in case studies of lung cancer, leukemia, and colorectal cancer, simulation results demonstrated that NBLDA can be a powerful tool for identifying potential lncRNA–disease associations as well.


Author(s):  
Xing Chen ◽  
Tian-Hao Li ◽  
Yan Zhao ◽  
Chun-Chun Wang ◽  
Chi-Chi Zhu

Abstract MicroRNA (miRNA) plays an important role in the occurrence, development, diagnosis and treatment of diseases. More and more researchers begin to pay attention to the relationship between miRNA and disease. Compared with traditional biological experiments, computational method of integrating heterogeneous biological data to predict potential associations can effectively save time and cost. Considering the limitations of the previous computational models, we developed the model of deep-belief network for miRNA-disease association prediction (DBNMDA). We constructed feature vectors to pre-train restricted Boltzmann machines for all miRNA-disease pairs and applied positive samples and the same number of selected negative samples to fine-tune DBN to obtain the final predicted scores. Compared with the previous supervised models that only use pairs with known label for training, DBNMDA innovatively utilizes the information of all miRNA-disease pairs during the pre-training process. This step could reduce the impact of too few known associations on prediction accuracy to some extent. DBNMDA achieves the AUC of 0.9104 based on global leave-one-out cross validation (LOOCV), the AUC of 0.8232 based on local LOOCV and the average AUC of 0.9048 ± 0.0026 based on 5-fold cross validation. These AUCs are better than other previous models. In addition, three different types of case studies for three diseases were implemented to demonstrate the accuracy of DBNMDA. As a result, 84% (breast neoplasms), 100% (lung neoplasms) and 88% (esophageal neoplasms) of the top 50 predicted miRNAs were verified by recent literature. Therefore, we could conclude that DBNMDA is an effective method to predict potential miRNA-disease associations.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Haochen Zhao ◽  
Linai Kuang ◽  
Lei Wang ◽  
Zhanwei Xuan

Recently, accumulating laboratorial studies have indicated that plenty of long noncoding RNAs (lncRNAs) play important roles in various biological processes and are associated with many complex human diseases. Therefore, developing powerful computational models to predict correlation between lncRNAs and diseases based on heterogeneous biological datasets will be important. However, there are few approaches to calculating and analyzing lncRNA-disease associations on the basis of information about miRNAs. In this article, a new computational method based on distance correlation set is developed to predict lncRNA-disease associations (DCSLDA). Comparing with existing state-of-the-art methods, we found that the major novelty of DCSLDA lies in the introduction of lncRNA-miRNA-disease network and distance correlation set; thus DCSLDA can be applied to predict potential lncRNA-disease associations without requiring any known disease-lncRNA associations. Simulation results show that DCSLDA can significantly improve previous existing models with reliable AUC of 0.8517 in the leave-one-out cross-validation. Furthermore, while implementing DCSLDA to prioritize candidate lncRNAs for three important cancers, in the first 0.5% of forecast results, 17 predicted associations are verified by other independent studies and biological experimental studies. Hence, it is anticipated that DCSLDA could be a great addition to the biomedical research field.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiechen Li ◽  
Xueyong Li ◽  
Xiang Feng ◽  
Bing Wang ◽  
Bihai Zhao ◽  
...  

Abstract Background In recent years, lncRNAs (long-non-coding RNAs) have been proved to be closely related to the occurrence and development of many serious diseases that are seriously harmful to human health. However, most of the lncRNA-disease associations have not been found yet due to high costs and time complexity of traditional bio-experiments. Hence, it is quite urgent and necessary to establish efficient and reasonable computational models to predict potential associations between lncRNAs and diseases. Results In this manuscript, a novel prediction model called TCSRWRLD is proposed to predict potential lncRNA-disease associations based on improved random walk with restart. In TCSRWRLD, a heterogeneous lncRNA-disease network is constructed first by combining the integrated similarity of lncRNAs and the integrated similarity of diseases. And then, for each lncRNA/disease node in the newly constructed heterogeneous lncRNA-disease network, it will establish a node set called TCS (Target Convergence Set) consisting of top 100 disease/lncRNA nodes with minimum average network distances to these disease/lncRNA nodes having known associations with itself. Finally, an improved random walk with restart is implemented on the heterogeneous lncRNA-disease network to infer potential lncRNA-disease associations. The major contribution of this manuscript lies in the introduction of the concept of TCS, based on which, the velocity of convergence of TCSRWRLD can be quicken effectively, since the walker can stop its random walk while the walking probability vectors obtained by it at the nodes in TCS instead of all nodes in the whole network have reached stable state. And Simulation results show that TCSRWRLD can achieve a reliable AUC of 0.8712 in the Leave-One-Out Cross Validation (LOOCV), which outperforms previous state-of-the-art results apparently. Moreover, case studies of lung cancer and leukemia demonstrate the satisfactory prediction performance of TCSRWRLD as well. Conclusions Both comparative results and case studies have demonstrated that TCSRWRLD can achieve excellent performances in prediction of potential lncRNA-disease associations, which imply as well that TCSRWRLD may be a good addition to the research of bioinformatics in the future.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260329
Author(s):  
Yi Zhang ◽  
Min Chen ◽  
Li Huang ◽  
Xiaolan Xie ◽  
Xin Li ◽  
...  

It is well known that numerous long noncoding RNAs (lncRNAs) closely relate to the physiological and pathological processes of human diseases and can serves as potential biomarkers. Therefore, lncRNA-disease associations that are identified by computational methods as the targeted candidates reduce the cost of biological experiments focusing on deep study furtherly. However, inaccurate construction of similarity networks and inadequate numbers of observed known lncRNA–disease associations, such inherent problems make many mature computational methods that have been developed for many years still exit some limitations. It motivates us to explore a new computational method that was fused with KATZ measure and space projection to fast probing potential lncRNA-disease associations (namely KATZSP). KATZSP is comprised of following key steps: combining all the global information with which to change Boolean network of known lncRNA–disease associations into the weighted networks; changing the similarities calculation into counting the number of walks that connect lncRNA nodes and disease nodes in bipartite graphs; obtaining the space projection scores to refine the primary prediction scores. The process to fuse KATZ measure and space projection was simplified and uncomplicated with needing only one attenuation factor. The leave-one-out cross validation (LOOCV) experimental results showed that, compared with other state-of-the-art methods (NCPLDA, LDAI-ISPS and IIRWR), KATZSP had a higher predictive accuracy shown with area-under-the-curve (AUC) value on the three datasets built, while KATZSP well worked on inferring potential associations related to new lncRNAs (or isolated diseases). The results from real cases study (such as pancreas cancer, lung cancer and colorectal cancer) further confirmed that KATZSP is capable of superior predictive ability to be applied as a guide for traditional biological experiments.


Author(s):  
Xing Chen ◽  
Lian-Gang Sun ◽  
Yan Zhao

Abstract Emerging evidence shows that microRNAs (miRNAs) play a critical role in diverse fundamental and important biological processes associated with human diseases. Inferring potential disease related miRNAs and employing them as the biomarkers or drug targets could contribute to the prevention, diagnosis and treatment of complex human diseases. In view of that traditional biological experiments cost much time and resources, computational models would serve as complementary means to uncover potential miRNA–disease associations. In this study, we proposed a new computational model named Neighborhood Constraint Matrix Completion for MiRNA–Disease Association prediction (NCMCMDA) to predict potential miRNA–disease associations. The main task of NCMCMDA was to recover the missing miRNA–disease associations based on the known miRNA–disease associations and integrated disease (miRNA) similarity. In this model, we innovatively integrated neighborhood constraint with matrix completion, which provided a novel idea of utilizing similarity information to assist the prediction. After the recovery task was transformed into an optimization problem, we solved it with a fast iterative shrinkage-thresholding algorithm. As a result, the AUCs of NCMCMDA in global and local leave-one-out cross validation were 0.9086 and 0.8453, respectively. In 5-fold cross validation, NCMCMDA achieved an average AUC of 0.8942 and standard deviation of 0.0015, which demonstrated NCMCMDA’s superior performance than many previous computational methods. Furthermore, NCMCMDA was applied to three different types of case studies to further evaluate its prediction reliability and accuracy. As a result, 84% (colon neoplasms), 98% (esophageal neoplasms) and 98% (breast neoplasms) of the top 50 predicted miRNAs were verified by recent literature.


2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Xiaoying Li ◽  
Yaping Lin ◽  
Changlong Gu ◽  
Zejun Li

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.


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