Yingli Zhong1, Ping Xuan1, Xiao Wang2, Tiangang Zhang3, Jianzhong Li1, Yong Liu1, Weixiong Zhang4,5. 1. School of Computer Science and Technology, Heilongjiang University, Harbin, China. 2. Department of Computer Science and Technology, Tsinghua University, Beijing, China. 3. School of Mathematical Science, Heilongjiang University, Harbin, China. 4. College of Math and Computer Science, Institute for Systems Biology, Jianghan University, Wuhan, China. 5. Department of Computer Science and Engineering, Washington University in St. Louis, Saint Louis, Missouri, USA.
Abstract
MOTIVATION: Identification of disease-associated miRNAs (disease miRNAs) is critical for understanding disease etiology and pathogenesis. Since miRNAs exert their functions by regulating the expression of their target mRNAs, several methods based on the target genes were proposed to predict disease miRNA candidates. They achieved only limited success as they all suffered from the high false-positive rate of target prediction results. Alternatively, other prediction methods were based on the observation that miRNAs with similar functions tend to be associated with similar diseases and vice versa. The methods exploited the information about miRNAs and diseases, including the functional similarities between miRNAs, the similarities between diseases, and the associations between miRNAs and diseases. However, how to integrate the multiple kinds of information completely and consider the biological characteristic of disease miRNAs is a challenging problem. RESULTS: We constructed a bilayer network to represent the complex relationships among miRNAs, among diseases and between miRNAs and diseases. We proposed a non-negative matrix factorization based method to rank, so as to predict, the disease miRNA candidates. The method integrated the miRNA functional similarity, the disease similarity and the miRNA-disease associations seamlessly, which exploited the complex relationships within the bilayer network and the consensus relationship between multiple kinds of information. Considering the correlation between the candidates related to various diseases, it predicted their respective candidates for all the diseases simultaneously. In addition, the sparseness characteristic of disease miRNAs was introduced to generate more reliable prediction model that excludes those noisy candidates. The results on 15 common diseases showed a superior performance of the new method for not only well-characterized diseases but also new ones. A detailed case study on breast neoplasms, colorectal neoplasms, lung neoplasms and 32 other diseases demonstrated the ability of the method for discovering potential disease miRNAs. AVAILABILITY AND IMPLEMENTATION: The web service for the new method and the list of predicted candidates for all the diseases are available at http://www.bioinfolab.top. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: Identification of disease-associated miRNAs (disease miRNAs) is critical for understanding disease etiology and pathogenesis. Since miRNAs exert their functions by regulating the expression of their target mRNAs, several methods based on the target genes were proposed to predict disease miRNA candidates. They achieved only limited success as they all suffered from the high false-positive rate of target prediction results. Alternatively, other prediction methods were based on the observation that miRNAs with similar functions tend to be associated with similar diseases and vice versa. The methods exploited the information about miRNAs and diseases, including the functional similarities between miRNAs, the similarities between diseases, and the associations between miRNAs and diseases. However, how to integrate the multiple kinds of information completely and consider the biological characteristic of disease miRNAs is a challenging problem. RESULTS: We constructed a bilayer network to represent the complex relationships among miRNAs, among diseases and between miRNAs and diseases. We proposed a non-negative matrix factorization based method to rank, so as to predict, the disease miRNA candidates. The method integrated the miRNA functional similarity, the disease similarity and the miRNA-disease associations seamlessly, which exploited the complex relationships within the bilayer network and the consensus relationship between multiple kinds of information. Considering the correlation between the candidates related to various diseases, it predicted their respective candidates for all the diseases simultaneously. In addition, the sparseness characteristic of disease miRNAs was introduced to generate more reliable prediction model that excludes those noisy candidates. The results on 15 common diseases showed a superior performance of the new method for not only well-characterized diseases but also new ones. A detailed case study on breast neoplasms, colorectal neoplasms, lung neoplasms and 32 other diseases demonstrated the ability of the method for discovering potential disease miRNAs. AVAILABILITY AND IMPLEMENTATION: The web service for the new method and the list of predicted candidates for all the diseases are available at http://www.bioinfolab.top. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Benjamin P Lewis; I-hung Shih; Matthew W Jones-Rhoades; David P Bartel; Christopher B Burge Journal: Cell Date: 2003-12-26 Impact factor: 41.582
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