Inferring novel lncRNA–disease associations based on a random walk model of a lncRNA functional similarity network

2014 ◽  
Vol 10 (8) ◽  
pp. 2074-2081 ◽  
Author(s):  
Jie Sun ◽  
Hongbo Shi ◽  
Zhenzhen Wang ◽  
Changjian Zhang ◽  
Lin Liu ◽  
...  

Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in the development of complex human diseases. Predicting novel human lncRNA–disease associations is a challenging and essential task.

Author(s):  
Hongying Zhao ◽  
Jian Shi ◽  
Yunpeng Zhang ◽  
Aimin Xie ◽  
Lei Yu ◽  
...  

Abstract Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.


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.


2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Liugen Wang ◽  
Min Shang ◽  
Qi Dai ◽  
Ping-an He

Abstract Background More and more evidence showed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human sophisticated diseases. Therefore, predicting human lncRNA-disease associations is a challenging and urgently task in bioinformatics to research of human sophisticated diseases. Results In the work, a global network-based computational framework called as LRWRHLDA were proposed which is a universal network-based method. Firstly, four isomorphic networks include lncRNA similarity network, disease similarity network, gene similarity network and miRNA similarity network were constructed. And then, six heterogeneous networks include known lncRNA-disease, lncRNA-gene, lncRNA-miRNA, disease-gene, disease-miRNA, and gene-miRNA associations network were applied to design a multi-layer network. Finally, the Laplace normalized random walk with restart algorithm in this global network is suggested to predict the relationship between lncRNAs and diseases. Conclusions The ten-fold cross validation is used to evaluate the performance of LRWRHLDA. As a result, LRWRHLDA achieves an AUC of 0.98402, which is higher than other compared methods. Furthermore, LRWRHLDA can predict isolated disease-related lnRNA (isolated lnRNA related disease). The results for colorectal cancer, lung adenocarcinoma, stomach cancer and breast cancer have been verified by other researches. The case studies indicated that our method is effective.


2018 ◽  
Vol 19 (11) ◽  
pp. 3410 ◽  
Author(s):  
Xiujuan Lei ◽  
Zengqiang Fang ◽  
Luonan Chen ◽  
Fang-Xiang Wu

CircRNAs have particular biological structure and have proven to play important roles in diseases. It is time-consuming and costly to identify circRNA-disease associations by biological experiments. Therefore, it is appealing to develop computational methods for predicting circRNA-disease associations. In this study, we propose a new computational path weighted method for predicting circRNA-disease associations. Firstly, we calculate the functional similarity scores of diseases based on disease-related gene annotations and the semantic similarity scores of circRNAs based on circRNA-related gene ontology, respectively. To address missing similarity scores of diseases and circRNAs, we calculate the Gaussian Interaction Profile (GIP) kernel similarity scores for diseases and circRNAs, respectively, based on the circRNA-disease associations downloaded from circR2Disease database (http://bioinfo.snnu.edu.cn/CircR2Disease/). Then, we integrate disease functional similarity scores and circRNA semantic similarity scores with their related GIP kernel similarity scores to construct a heterogeneous network made up of three sub-networks: disease similarity network, circRNA similarity network and circRNA-disease association network. Finally, we compute an association score for each circRNA-disease pair based on paths connecting them in the heterogeneous network to determine whether this circRNA-disease pair is associated. We adopt leave one out cross validation (LOOCV) and five-fold cross validations to evaluate the performance of our proposed method. In addition, three common diseases, Breast Cancer, Gastric Cancer and Colorectal Cancer, are used for case studies. Experimental results illustrate the reliability and usefulness of our computational method in terms of different validation measures, which indicates PWCDA can effectively predict potential circRNA-disease associations.


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):  
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.


2020 ◽  
Vol 15 ◽  
Author(s):  
Qingqi Zhu ◽  
Yongxian Fan ◽  
Xiaoyong Pan

Background: MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with about 22 nucleotides and they play a significant role in a variety of complex biological processes. Many researches have shown that miRNAs are closely related to human diseases. Although the biological experiments are reliable in identifying miRNA-disease associations, they are time-consuming and costly. Objective: Thus, computational methods are urgently needed to effectively predict miRNA-disease associations. Method: In this paper, we proposed a novel method, BIRWMDA based on a bi-random walk model to predict miRNAdisease associations. Specifically, in BIRWMDA, the similarity network fusion algorithm is used to combine the multiple similarity matrices to obtain a miRNA-miRNA similarity matrix and a disease-disease similarity matrix, then the miRNAdisease associations were predicted by the bi-random walk model. Results: To evaluate the performance of BIRWMDA, we ran the leave-one-out cross validation and 5-fold cross validation, and their corresponding AUCs were 0.9303 and 0.9223 ± 0.00067, respectively. To further demonstrate the effectiveness of the BIRWMDA, from the perspective of exploring disease-related miRNAs, we conducted three case studies of breast neoplasms, prostate neoplasms and gastric neoplasms, where 48, 50 and 50 out of the top 50 predicted miRNAs were confirmed by literatures, respectively. From the perspective of exploring miRNA-related diseases, we conducted two case studies of hsa-mir-21 and hsa-mir-155, where 7 and 5 out of the top 10 predicted diseases were confirmed by literatures, respectively. Conclusion: Fusion of multiple biological networks could effectively predict miRNA-diseases associations. We expected BIRWMDA to severe as a biological tool for mining potential miRNA-disease associations.


2021 ◽  
Vol 17 (7) ◽  
pp. e1009165
Author(s):  
Lei Li ◽  
Zhen Gao ◽  
Yu-Tian Wang ◽  
Ming-Wen Zhang ◽  
Jian-Cheng Ni ◽  
...  

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.


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