NCMCMDA: miRNA–disease association prediction through neighborhood constraint matrix completion

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.

2021 ◽  
Vol 16 ◽  
Author(s):  
Yayan Zhang ◽  
Guihua Duan ◽  
Cheng Yan ◽  
Haolun Yi ◽  
Fang-Xiang Wu ◽  
...  

Background: Increasing evidence has indicated that miRNA-disease association prediction plays a critical role in the study of clinical drugs. Researchers have proposed many computational models for miRNA-disease prediction. However, there is no unified platform to compare and analyze the pros and cons or share the code and data of these models. Objective: In this study, we develop an easy-to-use platform (MDAPlatform) to construct and assess miRNA-disease association prediction method. Methods: MDAPlatform integrates the relevant data of miRNA, disease and miRNA-disease associations that are used in previous miRNA-disease association prediction studies. Based on the componentized model, it develops differet components of previous computational methods. Results: Users can conduct cross validation experiments and compare their methods with other methods, and the visualized comparison results are also provided. Conclusion: Based on the componentized model, MDAPlatform provides easy-to-operate interfaces to construct the miRNA-disease association method, which is beneficial to develop new miRNA-disease association prediction methods in the future.


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.


2021 ◽  
Vol 21 (S1) ◽  
Author(s):  
Yu-Tian Wang ◽  
Qing-Wen Wu ◽  
Zhen Gao ◽  
Jian-Cheng Ni ◽  
Chun-Hou Zheng

Abstract Background MicroRNAs (miRNAs) have been confirmed to have close relationship with various human complex diseases. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases. However, it is still a big challenge to identify which miRNAs are related to diseases. As experimental methods are in general expensive and time‐consuming, it is important to develop efficient computational models to discover potential miRNA-disease associations. Methods This study presents a novel prediction method called HFHLMDA, which is based on high-dimensionality features and hypergraph learning, to reveal the association between diseases and miRNAs. Firstly, the miRNA functional similarity and the disease semantic similarity are integrated to form an informative high-dimensionality feature vector. Then, a hypergraph is constructed by the K-Nearest-Neighbor (KNN) method, in which each miRNA-disease pair and its k most relevant neighbors are linked as one hyperedge to represent the complex relationships among miRNA-disease pairs. Finally, the hypergraph learning model is designed to learn the projection matrix which is used to calculate uncertain miRNA-disease association score. Result Compared with four state-of-the-art computational models, HFHLMDA achieved best results of 92.09% and 91.87% in leave-one-out cross validation and fivefold cross validation, respectively. Moreover, in case studies on Esophageal neoplasms, Hepatocellular Carcinoma, Breast Neoplasms, 90%, 98%, and 96% of the top 50 predictions have been manually confirmed by previous experimental studies. Conclusion MiRNAs have complex connections with many human diseases. In this study, we proposed a novel computational model to predict the underlying miRNA-disease associations. All results show that the proposed method is effective for miRNA–disease association predication.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Han-Jing Jiang ◽  
Yu-An Huang ◽  
Zhu-Hong You

Computational drug repositioning, designed to identify new indications for existing drugs, significantly reduced the cost and time involved in drug development. Prediction of drug-disease associations is promising for drug repositioning. Recent years have witnessed an increasing number of machine learning-based methods for calculating drug repositioning. In this paper, a novel feature learning method based on Gaussian interaction profile kernel and autoencoder (GIPAE) is proposed for drug-disease association. In order to further reduce the computation cost, both batch normalization layer and the full-connected layer are introduced to reduce training complexity. The experimental results of 10-fold cross validation indicate that the proposed method achieves superior performance on Fdataset and Cdataset with the AUCs of 93.30% and 96.03%, respectively, which were higher than many previous computational models. To further assess the accuracy of GIPAE, we conducted case studies on two complex human diseases. The top 20 drugs predicted, 14 obesity-related drugs, and 11 drugs related to Alzheimer's disease were validated in the CTD database. The results of cross validation and case studies indicated that GIPAE is a reliable model for predicting drug-disease associations.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bailong Liu ◽  
Xiaoyan Zhu ◽  
Lei Zhang ◽  
Zhizheng Liang ◽  
Zhengwei Li

Abstract Background Cumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results. Results We present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA. Conclusions The performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.


Author(s):  
Yahui Long ◽  
Jiawei Luo ◽  
Yu Zhang ◽  
Yan Xia

Abstract Motivation human microbes play a critical role in an extensive range of complex human diseases and become a new target in precision medicine. In silico methods of identifying microbe–disease associations not only can provide a deep insight into understanding the pathogenic mechanism of complex human diseases but also assist pharmacologists to screen candidate targets for drug development. However, the majority of existing approaches are based on linear models or label propagation, which suffers from limitations in capturing nonlinear associations between microbes and diseases. Besides, it is still a great challenge for most previous methods to make predictions for new diseases (or new microbes) with few or without any observed associations. Results in this work, we construct features for microbes and diseases by fully exploiting multiply sources of biomedical data, and then propose a novel deep learning framework of graph attention networks with inductive matrix completion for human microbe-disease association prediction, named GATMDA. To our knowledge, this is the first attempt to leverage graph attention networks for this important task. In particular, we develop an optimized graph attention network with talking-heads to learn representations for nodes (i.e. microbes and diseases). To focus on more important neighbours and filter out noises, we further design a bi-interaction aggregator to enforce representation aggregation of similar neighbours. In addition, we combine inductive matrix completion to reconstruct microbe-disease associations to capture the complicated associations between diseases and microbes. Comprehensive experiments on two data sets (i.e. HMDAD and Disbiome) demonstrated that our proposed model consistently outperformed baseline methods. Case studies on two diseases, i.e. asthma and inflammatory bowel disease, further confirmed the effectiveness of our proposed model of GATMDA. Availability python codes and data set are available at: https://github.com/yahuilong/GATMDA. Contact [email protected].


Author(s):  
Lei Li ◽  
Zhen Gao ◽  
Chun-Hou Zheng ◽  
Yu Wang ◽  
Yu-Tian Wang ◽  
...  

MicroRNAs (miRNAs) that belong to non-coding RNAs are verified to be closely associated with several complicated biological processes and human diseases. In this study, we proposed a novel model that was Similarity Network Fusion and Inductive Matrix Completion for miRNA-Disease Association Prediction (SNFIMCMDA). We applied inductive matrix completion (IMC) method to acquire possible associations between miRNAs and diseases, which also could obtain corresponding correlation scores. IMC was performed based on the verified connections of miRNA–disease, miRNA similarity, and disease similarity. In addition, miRNA similarity and disease similarity were calculated by similarity network fusion, which could masterly integrate multiple data types to obtain target data. We integrated miRNA functional similarity and Gaussian interaction profile kernel similarity by similarity network fusion to obtain miRNA similarity. Similarly, disease similarity was integrated in this way. To indicate the utility and effectiveness of SNFIMCMDA, we both applied global leave-one-out cross-validation and five-fold cross-validation to validate our model. Furthermore, case studies on three significant human diseases were also implemented to prove the effectiveness of SNFIMCMDA. The results demonstrated that SNFIMCMDA was effective for prediction of possible associations of miRNA–disease.


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.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Guobo Xie ◽  
Zhiliang Fan ◽  
Yuping Sun ◽  
Cuiming Wu ◽  
Lei Ma

Abstract Background Recently, numerous biological experiments have indicated that microRNAs (miRNAs) play critical roles in exploring the pathogenesis of various human diseases. Since traditional experimental methods for miRNA-disease associations detection are costly and time-consuming, it becomes urgent to design efficient and robust computational techniques for identifying undiscovered interactions. Methods In this paper, we proposed a computation framework named weighted bipartite network projection for miRNA-disease association prediction (WBNPMD). In this method, transfer weights were constructed by combining the known miRNA and disease similarities, and the initial information was properly configured. Then the two-step bipartite network algorithm was implemented to infer potential miRNA-disease associations. Results The proposed WBNPMD was applied to the known miRNA-disease association data, and leave-one-out cross-validation (LOOCV) and fivefold cross-validation were implemented to evaluate the performance of WBNPMD. As a result, our method achieved the AUCs of 0.9321 and $$0.9173 \pm 0.0005$$ 0.9173 ± 0.0005 in LOOCV and fivefold cross-validation, and outperformed other four state-of-the-art methods. We also carried out two kinds of case studies on prostate neoplasm, colorectal neoplasm, and lung neoplasm, and most of the top 50 predicted miRNAs were confirmed to have an association with the corresponding diseases based on dbDeMC, miR2Disease, and HMDD V3.0 databases. Conclusions The experimental results demonstrate that WBNPMD can accurately infer potential miRNA-disease associations. We anticipated that the proposed WBNPMD could serve as a powerful tool for potential miRNA-disease associations excavation.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yahui Long ◽  
Jiawei Luo

Abstract Background An increasing number of biological and clinical evidences have indicated that the microorganisms significantly get involved in the pathological mechanism of extensive varieties of complex human diseases. Inferring potential related microbes for diseases can not only promote disease prevention, diagnosis and treatment, but also provide valuable information for drug development. Considering that experimental methods are expensive and time-consuming, developing computational methods is an alternative choice. However, most of existing methods are biased towards well-characterized diseases and microbes. Furthermore, existing computational methods are limited in predicting potential microbes for new diseases. Results Here, we developed a novel computational model to predict potential human microbe-disease associations (MDAs) based on Weighted Meta-Graph (WMGHMDA). We first constructed a heterogeneous information network (HIN) by combining the integrated microbe similarity network, the integrated disease similarity network and the known microbe-disease bipartite network. And then, we implemented iteratively pre-designed Weighted Meta-Graph search algorithm on the HIN to uncover possible microbe-disease pairs by cumulating the contribution values of weighted meta-graphs to the pairs as their probability scores. Depending on contribution potential, we described the contribution degree of different types of meta-graphs to a microbe-disease pair with bias rating. Meta-graph with higher bias rating will be assigned greater weight value when calculating probability scores. Conclusions The experimental results showed that WMGHMDA outperformed some state-of-the-art methods with average AUCs of 0.9288, 0.9068 ±0.0031 in global leave-one-out cross validation (LOOCV) and 5-fold cross validation (5-fold CV), respectively. In the case studies, 9, 19, 37 and 10, 20, 45 out of top-10, 20, 50 candidate microbes were manually verified by previous reports for asthma and inflammatory bowel disease (IBD), respectively. Furthermore, three common human diseases (Crohn’s disease, Liver cirrhosis, Type 1 diabetes) were adopted to demonstrate that WMGHMDA could be efficiently applied to make predictions for new diseases. In summary, WMGHMDA has a high potential in predicting microbe-disease associations.


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