Dataset Information

Multiple Linear Regression Analysis of lncRNA-Disease Association Prediction Based on Clinical Prognosis Data.

ABSTRACT: Long noncoding RNAs (lncRNAs) have an important role in various life processes of the body, especially cancer. The analysis of disease prognosis is ignored in current prediction on lncRNA-disease associations. In this study, a multiple linear regression model was constructed for lncRNA-disease association prediction based on clinical prognosis data (MlrLDAcp), which integrated the cancer data of clinical prognosis and the expression quantity of lncRNA transcript. MlrLDAcp could realize not only cancer survival prediction but also lncRNA-disease association prediction. Ultimately, 60 lncRNAs most closely related to prostate cancer survival were selected from 481 alternative lncRNAs. Then, the multiple linear regression relationship between the prognosis survival of 176 patients with prostate cancer and 60 lncRNAs was also given. Compared with previous studies, MlrLDAcp had a predominant survival predictive ability and could effectively predict lncRNA-disease associations. MlrLDAcp had an area under the curve (AUC) value of 0.875 for survival prediction and an AUC value of 0.872 for lncRNA-disease association prediction. It could be an effective biological method for biomedical research.

SUBMITTER: Wang B

PROVIDER: S-EPMC6311254 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Multiple Linear Regression Analysis of lncRNA-Disease Association Prediction Based on Clinical Prognosis Data.

Wang Bo B Zhang Jing J

BioMed research international 20181211

Long noncoding RNAs (lncRNAs) have an important role in various life processes of the body, especially cancer. The analysis of disease prognosis is ignored in current prediction on lncRNA-disease associations. In this study, a multiple linear regression model was constructed for lncRNA-disease association prediction based on clinical prognosis data (MlrLDAcp), which integrated the cancer data of clinical prognosis and the expression quantity of lncRNA transcript. MlrLDAcp could realize not only ...[more]

PMID: 30643802

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Project description:BackgroundOver the past decades, a large number of long non-coding RNAs (lncRNAs) have been identified. Growing evidence has indicated that the mutation and dysregulation of lncRNAs play a critical role in the development of many complex human diseases. Consequently, identifying potential disease-related lncRNAs is an effective means to improve the quality of disease diagnostics and treatment, which is the motivation of this work. Here, we propose a computational model (LncDisAP) for potential disease-related lncRNA identification based on multiple biological datasets. First, the associations between lncRNA and different data sources are collected from different databases. With these data sources as dimensions, we calculate the functional associations between lncRNAs by the recommendation strategy of collaborative filtering. Subsequently, a disease-associated lncRNA functional network is built with functional similarities between lncRNAs as the weight. Ultimately, potential disease-related lncRNAs can be identified based on ranked scores derived by random walking with restart (RWR). Then, training sets and testing sets are extracted from two different versions of a disease-lncRNA dataset to assess the performance of LncDisAP on 54 diseases.ResultsA lncRNA functional network is built based on the proposed computational model, and it contains 66,060 associations among 364 lncRNAs associated with 182 diseases in total. We extract 218 known disease-lncRNA pairs associated with 54 diseases to assess the network. As a result, the average AUC (area under the receiver operating characteristic curve) of LncDisAP is 78.08%.ConclusionIn this article, a computational model integrating multiple lncRNA-related biological datasets is proposed for identifying potential disease-related lncRNAs. The result shows that LncDisAP is successful in predicting novel disease-related lncRNA signatures. In addition, with several common cancers taken as case studies, we found some unknown lncRNAs that could be associated with these diseases through our network. These results suggest that this method can be helpful in improving the quality for disease diagnostics and treatment.

Project description:Nowadays, as more and more associations between microRNAs (miRNAs) and diseases have been discovered, miRNA has gradually become a hot topic in the biological field. Because of the high consumption of time and money on carrying out biological experiments, computational method which can help scientists choose the most likely associations between miRNAs and diseases for further experimental studies is desperately needed. In this study, we proposed a method of Graph Regression for MiRNA-Disease Association prediction (GRMDA) which combines known miRNA-disease associations, miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity. We used Gaussian interaction profile kernel similarity to supplement the shortage of miRNA functional similarity and disease semantic similarity. Furthermore, the graph regression was synchronously performed in three latent spaces, including association space, miRNA similarity space, and disease similarity space, by using two matrix factorization approaches called Singular Value Decomposition and Partial Least-Squares to extract important related attributes and filter the noise. In the leave-one-out cross validation and five-fold cross validation, GRMDA obtained the AUCs of 0.8272 and 0.8080 ± 0.0024, respectively. Thus, its performance is better than some previous models. In the case study of Lymphoma using the recorded miRNA-disease associations in HMDD V2.0 database, 88% of top 50 predicted miRNAs were verified by experimental literatures. In order to test the performance of GRMDA on new diseases with no known related miRNAs, we took Breast Neoplasms as an example by regarding all the known related miRNAs as unknown ones. We found that 100% of top 50 predicted miRNAs were verified. Moreover, 84% of top 50 predicted miRNAs in case study for Esophageal Neoplasms based on HMDD V1.0 were verified to have known associations. In conclusion, GRMDA is an effective and practical method for miRNA-disease association prediction.

Project description:BackgroundIn recent years, increasing evidences have indicated that long non-coding RNAs (lncRNAs) are deeply involved in a wide range of human biological pathways. The mutations and disorders of lncRNAs are closely associated with many human diseases. Therefore, it is of great importance to predict potential associations between lncRNAs and complex diseases for the diagnosis and cure of complex diseases. However, the functional mechanisms of the majority of lncRNAs are still remain unclear. As a result, it remains a great challenge to predict potential associations between lncRNAs and diseases.ResultsHere, we proposed a new method to predict potential lncRNA-disease associations. First, we constructed a bipartite network based on known associations between diseases and lncRNAs/protein coding genes. Then the cluster association scores were calculated to evaluate the strength of the inner relationships between disease clusters and gene clusters. Finally, the gene-disease association scores are defined based on disease-gene cluster association scores and used to measure the strength for potential gene-disease associations.ConclusionsLeave-One Out Cross Validation (LOOCV) and 5-fold cross validation tests were implemented to evaluate the performance of our method. As a result, our method achieved reliable performance in the LOOCV (AUCs of 0.8169 and 0.8410 based on Yang's dataset and Lnc2cancer 2.0 database, respectively), and 5-fold cross validation (AUCs of 0.7573 and 0.8198 based on Yang's dataset and Lnc2cancer 2.0 database, respectively), which were significantly higher than the other three comparative methods. Furthermore, our method is simple and efficient. Only the known gene-disease associations are exploited in a graph manner and further new gene-disease associations can be easily incorporated in our model. The results for melanoma and ovarian cancer have been verified by other researches. The case studies indicated that our method can provide informative clues for further investigation.

Dataset Information

Multiple Linear Regression Analysis of lncRNA-Disease Association Prediction Based on Clinical Prognosis Data.

Publications

Multiple Linear Regression Analysis of lncRNA-Disease Association Prediction Based on Clinical Prognosis Data.

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