A novel semi-supervised model for miRNA-disease association prediction based on \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{d

BackgroundIdentification of miRNA-disease associations has attracted much attention recently due to the functional roles of miRNAs implicated in various biological and pathological processes. Great efforts have been made to discover the potential associations between miRNAs and diseases both experimentally and computationally. Although reliable, the experimental methods are in general time-consuming and labor-intensive. In comparison, computational methods are more efficient and applicable to large-scale datasets.MethodsIn this paper, we propose a novel semi-supervised model to predict miRNA-disease associations via $$\ell_{1}$$ℓ1-norm graph. Specifically, we first recalculate the miRNA functional similarities as well as the disease semantic similarities based on the latest version of MeSH descriptors and HMDD. We then update the similarity matrices and association matrix iteratively in both miRNA space and disease space. The optimized association matrices from each space are combined together as the final output.ResultsCompared with four state-of-the-art prediction methods, our method achieved favorable performance with AUCs of 0.943 and 0.946 in both global LOOCV and local LOOCV, respectively. In addition, we carried out three types of case studies on five common human diseases, and most of the top 50 predicted miRNAs were confirmed to be associated with the investigated diseases by four databases dbDEMC, PheomiR, miR2Disease and miRwayDB. Specifically, our results provided potential evidence that miRNAs within the same family or cluster were likely to play functional roles together in given diseases.ConclusionsTaken together, the experimental results clearly demonstrated the utility of the proposed method. We anticipated that our method could serve as a reliable and efficient tool for miRNA-disease association prediction.

[1]  K. Reddy,et al.  MicroRNA (miRNA) in cancer , 2015, Cancer Cell International.

[2]  Cheng Liang,et al.  A Discriminative Feature Extraction Approach for Tumor Classification Using Gene Expression Data , 2016 .

[3]  Huanqing Feng,et al.  NTSMDA: prediction of miRNA-disease associations by integrating network topological similarity. , 2016, Molecular bioSystems.

[4]  H. Osada,et al.  let‐7 and miR‐17‐92: Small‐sized major players in lung cancer development , 2011, Cancer science.

[5]  Xing Chen,et al.  RWRMDA: predicting novel human microRNA-disease associations. , 2012, Molecular bioSystems.

[6]  Jan Gorodkin,et al.  Protein-driven inference of miRNA–disease associations , 2013, Bioinform..

[7]  Shesh N. Rai,et al.  Micro-RNA-186-5p inhibition attenuates proliferation, anchorage independent growth and invasion in metastatic prostate cancer cells , 2018, BMC Cancer.

[8]  J. Zhang,et al.  miR-200bc/429 cluster targets PLCγ1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer , 2010, Oncogene.

[9]  Yadong Wang,et al.  Predicting human microRNA-disease associations based on support vector machine , 2010, 2010 IEEE International Conference on Bioinformatics and Biomedicine (BIBM).

[10]  Zhaolei Zhang,et al.  SNPdryad: predicting deleterious non-synonymous human SNPs using only orthologous protein sequences , 2014, Bioinform..

[11]  Ana Kozomara,et al.  miRBase: annotating high confidence microRNAs using deep sequencing data , 2013, Nucleic Acids Res..

[12]  Xiangxiang Zeng,et al.  Inferring MicroRNA-Disease Associations by Random Walk on a Heterogeneous Network with Multiple Data Sources , 2017, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[13]  Nan Zhang,et al.  MicroRNA-197 induces epithelial–mesenchymal transition and invasion through the downregulation of HIPK2 in lung adenocarcinoma , 2018, Journal of Genetics.

[14]  C. Pasquier,et al.  Prediction of miRNA-disease associations with a vector space model , 2016, Scientific Reports.

[15]  Laiyi Fu,et al.  A deep ensemble model to predict miRNA-disease association , 2017, Scientific Reports.

[16]  Xia Li,et al.  Prediction of potential disease-associated microRNAs based on random walk , 2015, Bioinform..

[17]  Xia Li,et al.  Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes , 2013, BMC Systems Biology.

[18]  Xiangxiang Zeng,et al.  Integrative approaches for predicting microRNA function and prioritizing disease-related microRNA using biological interaction networks , 2016, Briefings Bioinform..

[19]  Aamir Ahmad,et al.  MicroRNAs in breast cancer therapy. , 2014, Current pharmaceutical design.

[20]  Jing Li,et al.  dbDEPC 2.0: updated database of differentially expressed proteins in human cancers , 2011, Nucleic Acids Res..

[21]  Xing Chen,et al.  PBMDA: A novel and effective path-based computational model for miRNA-disease association prediction , 2017, PLoS Comput. Biol..

[22]  Tadashi Kimura,et al.  The Role of MicroRNAs in Ovarian Cancer , 2014, BioMed research international.

[23]  Xing Chen,et al.  NDAMDA: Network distance analysis for MiRNA‐disease association prediction , 2018, Journal of cellular and molecular medicine.

[24]  Mark S. Litwin,et al.  The Diagnosis and Treatment of Prostate Cancer: A Review , 2017, JAMA.

[25]  Lei Zhu,et al.  Unsupervised Visual Hashing with Semantic Assistant for Content-Based Image Retrieval , 2017, IEEE Transactions on Knowledge and Data Engineering.

[26]  Peng Ru,et al.  miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial–Mesenchymal Transition Signaling , 2012, Molecular Cancer Therapeutics.

[27]  Rajarshi Guha,et al.  Large-scale screening identifies a novel microRNA, miR-15a-3p, which induces apoptosis in human cancer cell lines , 2013, RNA biology.

[28]  Yang Li,et al.  HMDD v2.0: a database for experimentally supported human microRNA and disease associations , 2013, Nucleic Acids Res..

[29]  Yufei Huang,et al.  Prediction of microRNAs Associated with Human Diseases Based on Weighted k Most Similar Neighbors , 2013, PloS one.

[30]  Lei Zhu,et al.  Unsupervised Topic Hypergraph Hashing for Efficient Mobile Image Retrieval , 2017, IEEE Transactions on Cybernetics.

[31]  Feiping Nie,et al.  Unsupervised and semi-supervised learning via ℓ1-norm graph , 2011, 2011 International Conference on Computer Vision.

[32]  Fabian J Theis,et al.  PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes , 2010, Genome Biology.

[33]  Na-Na Guan,et al.  GIMDA: Graphlet interaction‐based MiRNA‐disease association prediction , 2017, Journal of cellular and molecular medicine.

[34]  Gerardo Botti,et al.  Micrornas in prostate cancer: an overview , 2017, Oncotarget.

[35]  S. Lawler,et al.  MicroRNAs in cancer: biomarkers, functions and therapy. , 2014, Trends in molecular medicine.

[36]  Xing Chen,et al.  Semi-supervised learning for potential human microRNA-disease associations inference , 2014, Scientific Reports.

[37]  Yadong Wang,et al.  Prioritization of disease microRNAs through a human phenome-microRNAome network , 2010, BMC Systems Biology.

[38]  Cheng Liang,et al.  A Novel Method to Detect Functional microRNA Regulatory Modules by Bicliques Merging , 2016, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[39]  Zhaolei Zhang,et al.  A probabilistic approach to explore human miRNA targetome by integrating miRNA-overexpression data and sequence information , 2014, Bioinform..

[40]  Xing Chen,et al.  EGBMMDA: Extreme Gradient Boosting Machine for MiRNA-Disease Association prediction , 2018, Cell Death & Disease.

[41]  Cheng Liang,et al.  Collective Prediction of Disease-Associated miRNAs Based on Transduction Learning , 2017, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[42]  D. Fishman,et al.  microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial–mesenchymal transition , 2014, Nature Communications.

[43]  Ream Langhe,et al.  microRNA and Ovarian Cancer. , 2015, Advances in experimental medicine and biology.

[44]  Xing Chen,et al.  HGIMDA: Heterogeneous graph inference for miRNA-disease association prediction , 2016, Oncotarget.

[45]  Kyungsook Han,et al.  miRNA-Disease Association Prediction with Collaborative Matrix Factorization , 2017, Complex..

[46]  Jiajun Yin,et al.  MicroRNA-337 regulates the PI3K/AKT and Wnt/β-catenin signaling pathways to inhibit hepatocellular carcinoma progression by targeting high-mobility group AT-hook 2. , 2018, American journal of cancer research.

[47]  Li Jia,et al.  MiR‐193a‐3p and miR‐224 mediate renal cell carcinoma progression by targeting alpha‐2,3‐sialyltransferase IV and the phosphatidylinositol 3 kinase/Akt pathway , 2018, Molecular carcinogenesis.

[48]  Wei Wu MicroRNA and Cancer , 2011, Methods in Molecular Biology.

[49]  Qionghai Dai,et al.  WBSMDA: Within and Between Score for MiRNA-Disease Association prediction , 2016, Scientific Reports.

[50]  Xing Chen,et al.  MKRMDA: multiple kernel learning-based Kronecker regularized least squares for MiRNA–disease association prediction , 2017, Journal of Translational Medicine.

[51]  Xing-Ming Zhao,et al.  Identifying cancer-related microRNAs based on gene expression data , 2015, Bioinform..

[52]  Supriyo Chakraborty,et al.  Role of miRNAs in lung cancer. , 2018, Journal of cellular physiology.

[53]  Liquan Xiao,et al.  On the Shoulders of Giants: Incremental Influence Maximization in Evolving Social Networks , 2015, Complex..

[54]  Cheng Liang,et al.  A graph regularized non-negative matrix factorization method for identifying microRNA-disease associations , 2018, Bioinform..

[55]  Wei Tang,et al.  dbDEMC 2.0: updated database of differentially expressed miRNAs in human cancers , 2016, Nucleic Acids Res..

[56]  Yadong Wang,et al.  miR2Disease: a manually curated database for microRNA deregulation in human disease , 2008, Nucleic Acids Res..

[57]  Xing Chen,et al.  MicroRNAs and complex diseases: from experimental results to computational models , 2019, Briefings Bioinform..

[58]  Dong Wang,et al.  Inferring the human microRNA functional similarity and functional network based on microRNA-associated diseases , 2010, Bioinform..

[59]  Pritam Saha,et al.  miRwayDB: a database for experimentally validated microRNA-pathway associations in pathophysiological conditions , 2018, Database J. Biol. Databases Curation.