A Probabilistic Matrix Factorization Method for Identifying lncRNA-disease Associations

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.

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A Novel Network-Based Computational Model for Prediction of Potential LncRNA–Disease Association

International Journal of Molecular Sciences ◽

10.3390/ijms20071549 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1549 ◽

Cited By ~ 6

Author(s):

Yang Liu ◽

Xiang Feng ◽

Haochen Zhao ◽

Zhanwei Xuan ◽

Lei Wang

Keyword(s):

Computational Models ◽

Disease Association ◽

Label Propagation ◽

Human Diseases ◽

Weighted Matrix ◽

Disease Associations ◽

Resource Allocation Strategy ◽

Simulation Results ◽

Leave One Out ◽

Treatment Prognosis

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.

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

Cells ◽

10.3390/cells9040881 ◽

2020 ◽

Vol 9 (4) ◽

pp. 881 ◽

Cited By ~ 1

Author(s):

Jihwan Ha ◽

Chihyun Park ◽

Chanyoung Park ◽

Sanghyun Park

Keyword(s):

Computational Models ◽

Matrix Completion ◽

Area Under The Curve ◽

Excellent Performance ◽

Novel Mirna ◽

Lack Of Information ◽

Disease Associations ◽

Roc Area ◽

Leave One Out ◽

Global And Local

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.

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Deep-belief network for predicting potential miRNA-disease associations

Briefings in Bioinformatics ◽

10.1093/bib/bbaa186 ◽

2020 ◽

Author(s):

Xing Chen ◽

Tian-Hao Li ◽

Yan Zhao ◽

Chun-Chun Wang ◽

Chi-Chi Zhu

Keyword(s):

Computational Models ◽

Cross Validation ◽

Biological Data ◽

Deep Belief Network ◽

Computational Method ◽

Restricted Boltzmann Machines ◽

Belief Network ◽

Disease Associations ◽

Leave One Out ◽

The Impact

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.

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A Novel Approach for Predicting Disease-lncRNA Associations Based on the Distance Correlation Set and Information of the miRNAs

Computational and Mathematical Methods in Medicine ◽

10.1155/2018/6747453 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Haochen Zhao ◽

Linai Kuang ◽

Lei Wang ◽

Zhanwei Xuan

Keyword(s):

Computational Models ◽

State Of The Art ◽

Experimental Studies ◽

Research Field ◽

Computational Method ◽

Biological Processes ◽

Distance Correlation ◽

Novel Approach ◽

Disease Associations ◽

Leave One Out

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.

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A novel target convergence set based random walk with restart for prediction of potential LncRNA-disease associations

BMC Bioinformatics ◽

10.1186/s12859-019-3216-4 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Jiechen Li ◽

Xueyong Li ◽

Xiang Feng ◽

Bing Wang ◽

Bihai Zhao ◽

...

Keyword(s):

Random Walk ◽

Case Studies ◽

Computational Models ◽

Stable State ◽

Random Walk With Restart ◽

Disease Network ◽

Disease Associations ◽

Novel Target ◽

Comparative Results ◽

Leave One Out

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.

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Adaptive boosting-based computational model for predicting potential miRNA-disease associations

Bioinformatics ◽

10.1093/bioinformatics/btz297 ◽

2019 ◽

Vol 35 (22) ◽

pp. 4730-4738 ◽

Cited By ~ 23

Author(s):

Yan Zhao ◽

Xing Chen ◽

Jun Yin

Keyword(s):

Computational Models ◽

Cross Validation ◽

Learning Algorithm ◽

Area Under The Curve ◽

Human Diseases ◽

Supplementary Information ◽

Weak Classifier ◽

Adaptive Boosting ◽

Disease Associations ◽

Leave One Out

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.

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A Novel Model for Predicting LncRNA-disease Associations based on the LncRNA-MiRNA-Disease Interactive Network

Current Bioinformatics ◽

10.2174/1574893613666180703105258 ◽

2019 ◽

Vol 14 (3) ◽

pp. 269-278 ◽

Cited By ~ 7

Author(s):

Lei Wang ◽

Zhanwei Xuan ◽

Shunxian Zhou ◽

Linai Kuang ◽

Tingrui Pei

Keyword(s):

Computational Models ◽

Close Association ◽

Experimental Studies ◽

Research Field ◽

Interactive Network ◽

Proposed Model ◽

Disease Associations ◽

Previous State ◽

Novel Method ◽

Leave One Out

Background: Accumulating experimental studies have manifested that long-non-coding RNAs (lncRNAs) play an important part in various biological process. It has been shown that their alterations and dysregulations are closely related to many critical complex diseases. Objective: It is of great importance to develop effective computational models for predicting potential lncRNA-disease associations. Method: Based on the hypothesis that there would be potential associations between a lncRNA and a disease if both of them have associations with the same group of microRNAs, and similar diseases tend to be in close association with functionally similar lncRNAs. A novel method for calculating similarities of both lncRNAs and diseases is proposed, and then a novel prediction model LDLMD for inferring potential lncRNA-disease associations is proposed. Results: LDLMD can achieve an AUC of 0.8925 in the Leave-One-Out Cross Validation (LOOCV), which demonstrated that the newly proposed model LDLMD significantly outperforms previous state-of-the-art methods and could be a great addition to the biomedical research field. Conclusion: Here, we present a new method for predicting lncRNA-disease associations, moreover, the method of our present decrease the time and cost of biological experiments.

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Predicting MiRNA-disease associations by multiple meta-paths fusion graph embedding model

BMC Bioinformatics ◽

10.1186/s12859-020-03765-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Lei Zhang ◽

Bailong Liu ◽

Zhengwei Li ◽

Xiaoyan Zhu ◽

Zhizhen Liang ◽

...

Keyword(s):

Computational Models ◽

Cross Validation ◽

Complex Structure ◽

Graph Embedding ◽

Prostate Neoplasms ◽

Prediction Performance ◽

Linear Transformations ◽

Disease Associations ◽

Meta Path ◽

Leave One Out

Abstract Background Many studies prove that miRNAs have significant roles in diagnosing and treating complex human diseases. However, conventional biological experiments are too costly and time-consuming to identify unconfirmed miRNA-disease associations. Thus, computational models predicting unidentified miRNA-disease pairs in an efficient way are becoming promising research topics. Although existing methods have performed well to reveal unidentified miRNA-disease associations, more work is still needed to improve prediction performance. Results In this work, we present a novel multiple meta-paths fusion graph embedding model to predict unidentified miRNA-disease associations (M2GMDA). Our method takes full advantage of the complex structure and rich semantic information of miRNA-disease interactions in a self-learning way. First, a miRNA-disease heterogeneous network was derived from verified miRNA-disease pairs, miRNA similarity and disease similarity. All meta-path instances connecting miRNAs with diseases were extracted to describe intrinsic information about miRNA-disease interactions. Then, we developed a graph embedding model to predict miRNA-disease associations. The model is composed of linear transformations of miRNAs and diseases, the means encoder of a single meta-path instance, the attention-aware encoder of meta-path type and attention-aware multiple meta-path fusion. We innovatively integrated meta-path instances, meta-path based neighbours, intermediate nodes in meta-paths and more information to strengthen the prediction in our model. In particular, distinct contributions of different meta-path instances and meta-path types were combined with attention mechanisms. The data sets and source code that support the findings of this study are available at https://github.com/dangdangzhang/M2GMDA. Conclusions M2GMDA achieved AUCs of 0.9323 and 0.9182 in global leave-one-out cross validation and fivefold cross validation with HDMM V2.0. The results showed that our method outperforms other prediction methods. Three kinds of case studies with lung neoplasms, breast neoplasms, prostate neoplasms, pancreatic neoplasms, lymphoma and colorectal neoplasms demonstrated that 47, 50, 49, 48, 50 and 50 out of the top 50 candidate miRNAs predicted by M2GMDA were validated by biological experiments. Therefore, it further confirms the prediction performance of our method.

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RCMF: a robust collaborative matrix factorization method to predict miRNA-disease associations

BMC Bioinformatics ◽

10.1186/s12859-019-3260-0 ◽

2019 ◽

Vol 20 (S25) ◽

Cited By ~ 3

Author(s):

Zhen Cui ◽

Jin-Xing Liu ◽

Ying-Lian Gao ◽

Chun-Hou Zheng ◽

Juan Wang

Keyword(s):

Matrix Factorization ◽

Factorization Method ◽

Simulation Experiments ◽

Gold Standard Dataset ◽

Disease Associations ◽

Auc Value ◽

Accuracy Of Prediction ◽

Fold Cross Validation ◽

Novel Associations ◽

Better Than

Abstract Background Predicting miRNA-disease associations (MDAs) is time-consuming and expensive. It is imminent to improve the accuracy of prediction results. So it is crucial to develop a novel computing technology to predict new MDAs. Although some existing methods can effectively predict novel MDAs, there are still some shortcomings. Especially when the disease matrix is processed, its sparsity is an important factor affecting the final results. Results A robust collaborative matrix factorization (RCMF) is proposed to predict novel MDAs. The L2,1-norm are introduced to our method to achieve the highest AUC value than other advanced methods. Conclusions 5-fold cross validation is used to evaluate our method, and simulation experiments are used to predict novel associations on Gold Standard Dataset. Finally, our prediction accuracy is better than other existing advanced methods. Therefore, our approach is effective and feasible in predicting novel MDAs.

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Genetic Interactions Effects of Cardiovascular Disorder Using Computational Models: A Review

Current Biotechnology ◽

10.2174/2211550109999201008125800 ◽

2020 ◽

Vol 9 (3) ◽

pp. 177-191

Author(s):

Sridharan Priya ◽

Radha K. Manavalan

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Diseases ◽

Computational Models ◽

Genetic Interaction ◽

Association Studies ◽

Genetic Interactions ◽

Computational Techniques ◽

Genome Wide Association Studies ◽

Artery Disease

Background: The diseases in the heart and blood vessels such as heart attack, Coronary Artery Disease, Myocardial Infarction (MI), High Blood Pressure, and Obesity, are generally referred to as Cardiovascular Diseases (CVD). The risk factors of CVD include gender, age, cholesterol/ LDL, family history, hypertension, smoking, and genetic and environmental factors. Genome- Wide Association Studies (GWAS) focus on identifying the genetic interactions and genetic architectures of CVD. Objective: Genetic interactions or Epistasis infer the interactions between two or more genes where one gene masks the traits of another gene and increases the susceptibility of CVD. To identify the Epistasis relationship through biological or laboratory methods needs an enormous workforce and more cost. Hence, this paper presents the review of various statistical and Machine learning approaches so far proposed to detect genetic interaction effects for the identification of various Cardiovascular diseases such as Coronary Artery Disease (CAD), MI, Hypertension, HDL and Lipid phenotypes data, and Body Mass Index dataset. Conclusion: This study reveals that various computational models identified the candidate genes such as AGT, PAI-1, ACE, PTPN22, MTHR, FAM107B, ZNF107, PON1, PON2, GTF2E1, ADGRB3, and FTO, which play a major role in genetic interactions for the causes of CVDs. The benefits, limitations, and issues of the various computational techniques for the evolution of epistasis responsible for cardiovascular diseases are exhibited.

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