Prioritization of disease microRNAs through a human phenome-microRNAome network

BackgroundThe identification of disease-related microRNAs is vital for understanding the pathogenesis of diseases at the molecular level, and is critical for designing specific molecular tools for diagnosis, treatment and prevention. Experimental identification of disease-related microRNAs poses considerable difficulties. Computational analysis of microRNA-disease associations is an important complementary means for prioritizing microRNAs for further experimental examination.ResultsHerein, we devised a computational model to infer potential microRNA-disease associations by prioritizing the entire human microRNAome for diseases of interest. We tested the model on 270 known experimentally verified microRNA-disease associations and achieved an area under the ROC curve of 75.80%. Moreover, we demonstrated that the model is applicable to diseases with which no known microRNAs are associated. The microRNAome-wide prioritization of microRNAs for 1,599 disease phenotypes is publicly released to facilitate future identification of disease-related microRNAs.ConclusionsWe presented a network-based approach that can infer potential microRNA-disease associations and drive testable hypotheses for the experimental efforts to identify the roles of microRNAs in human diseases.

[1]  Domenico Coppola,et al.  MicroRNA-221/222 Negatively Regulates Estrogen Receptorα and Is Associated with Tamoxifen Resistance in Breast Cancer* , 2008, Journal of Biological Chemistry.

[2]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[3]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[4]  M. Oti,et al.  The modular nature of genetic diseases , 2006, Clinical genetics.

[5]  P. Bork,et al.  G2D: a tool for mining genes associated with disease , 2005, BMC Genetics.

[6]  David J. Porteous,et al.  Speeding disease gene discovery by sequence based candidate prioritization , 2005, BMC Bioinformatics.

[7]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[8]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

[9]  Yi Xing,et al.  The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease , 2008, The Journal of Neuroscience.

[10]  Q. Cui,et al.  An Analysis of Human MicroRNA and Disease Associations , 2008, PloS one.

[11]  B. Snel,et al.  Predicting disease genes using protein–protein interactions , 2006, Journal of Medical Genetics.

[12]  Lin Zhang,et al.  The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis , 2008, Nature Cell Biology.

[13]  Mircea Ivan,et al.  MicroRNA regulation of DNA repair gene expression in hypoxic stress. , 2009, Cancer research.

[14]  E. Snitkin,et al.  Genome-wide prioritization of disease genes and identification of disease-disease associations from an integrated human functional linkage network , 2009, Genome Biology.

[15]  Jason Y. Liu,et al.  Analysis of protein sequence and interaction data for candidate disease gene prediction , 2006, Nucleic acids research.

[16]  Illés J. Farkas,et al.  Human microRNAs co-silence in well-separated groups and have different predicted essentialities , 2009, Bioinform..

[17]  Bassem A. Hassan,et al.  Gene prioritization through genomic data fusion , 2006, Nature Biotechnology.

[18]  P. Bork,et al.  Association of genes to genetically inherited diseases using data mining , 2002, Nature Genetics.

[19]  P. Radivojac,et al.  An integrated approach to inferring gene–disease associations in humans , 2008, Proteins.

[20]  P. Robinson,et al.  Walking the interactome for prioritization of candidate disease genes. , 2008, American journal of human genetics.

[21]  Michael Q. Zhang,et al.  Network-based global inference of human disease genes , 2008, Molecular systems biology.

[22]  P. Aloy,et al.  A network medicine approach to human disease , 2009, FEBS letters.

[23]  R. Duisters,et al.  MIRNA-133 AND MIRNA-30 REGULATE CONNECTIVE TISSUE GROWTH FACTOR: IMPLICATIONS FOR A ROLE OF MIRNAS IN MYOCARDIAL MATRIX REMODELING , 2013 .

[24]  David J. Porteous,et al.  SUSPECTS : enabling fast and effective prioritization of positional candidates , 2005 .

[25]  Tyler E. Miller,et al.  MicroRNA-221/222 Confers Tamoxifen Resistance in Breast Cancer by Targeting p27Kip1*♦ , 2008, Journal of Biological Chemistry.

[26]  Robert A. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer (Nature (2007) 449, (682-688)) , 2008 .

[27]  Bart De Moor,et al.  Erratum: Gene prioritization through genomic data fusion , 2006, Nature Biotechnology.

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

[29]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[30]  Pall I. Olason,et al.  A human phenome-interactome network of protein complexes implicated in genetic disorders , 2007, Nature Biotechnology.

[31]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[32]  Henry Horng-Shing Lu,et al.  Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes , 2009, PLoS Comput. Biol..

[33]  Rosario M. Piro,et al.  Prediction of Human Disease Genes by Human-Mouse Conserved Coexpression Analysis , 2008, PLoS Comput. Biol..

[34]  Tasneem Motiwala,et al.  Down-regulation of Micro-RNA-1 (miR-1) in Lung Cancer , 2008, Journal of Biological Chemistry.

[35]  M. Huynen,et al.  Phenome connections. , 2008, Trends in genetics : TIG.

[36]  Nitai P. Bhattacharyya,et al.  MicroRNA Interaction network in human: implications of clustered microRNA in biological pathways and genetic diseases , 2009, 0901.4211.

[37]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[38]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[39]  R. Sharan,et al.  Protein networks in disease. , 2008, Genome research.

[40]  XU JIANZHEN,et al.  microRNA clusters A computational screen for mouse signaling pathways targeted by Material Supplemental , 2022 .

[41]  Aimee L Jackson,et al.  Coordinated regulation of cell cycle transcripts by p53-Inducible microRNAs, miR-192 and miR-215. , 2008, Cancer research.

[42]  F. Slack,et al.  The let-7 microRNA reduces tumor growth in mouse models of lung cancer , 2008, Cell cycle.

[43]  Sung-Liang Yu,et al.  MicroRNA signature predicts survival and relapse in lung cancer. , 2008, Cancer cell.

[44]  Karen L. Mohlke,et al.  Data and text mining A computational system to select candidate genes for complex human traits , 2007 .

[45]  M. Wood,et al.  Short non-coding RNA biology and neurodegenerative disorders: novel disease targets and therapeutics. , 2009, Human molecular genetics.

[46]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[47]  John W M Martens,et al.  Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer , 2008, Proceedings of the National Academy of Sciences.

[48]  Gerard J. Nuovo,et al.  Erratum: Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1 (Journal of Biological Chemistry (2018) 293 (33394–33405) DOI: 10.1074/jbc.M804788200) , 2008 .

[49]  A. Barabasi,et al.  Network medicine--from obesity to the "diseasome". , 2007, The New England journal of medicine.

[50]  C. Ouzounis,et al.  Genome-wide identification of genes likely to be involved in human genetic disease. , 2004, Nucleic acids research.

[51]  Alan F. Scott,et al.  Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders , 2002, Nucleic Acids Res..

[52]  F. Slack,et al.  MicroRNA in cancer prognosis. , 2008, The New England journal of medicine.

[53]  G. Vriend,et al.  A text-mining analysis of the human phenome , 2006, European Journal of Human Genetics.

[54]  Chaoqian Xu,et al.  The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 , 2011, Nature Medicine.

[55]  Mikhail Pachkov,et al.  MicroRNA-221–222 Regulate the Cell Cycle in Mast Cells1 , 2009, The Journal of Immunology.

[56]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[57]  K. Ohshiro,et al.  MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. , 2008, Cancer research.

[58]  C. Wijmenga,et al.  Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes. , 2006, American journal of human genetics.

[59]  Vassilis Georgoulias,et al.  Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. , 2008, Clinical chemistry.

[60]  Yunlong Liu,et al.  Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance , 2009, Bioinform..

[61]  William A Robinson,et al.  Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma. , 2008, Blood.

[62]  Christina Thaller,et al.  miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis , 2008, Nature Neuroscience.

[63]  Y. Benjamini,et al.  THE CONTROL OF THE FALSE DISCOVERY RATE IN MULTIPLE TESTING UNDER DEPENDENCY , 2001 .

[64]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[65]  Jan Freudenberg,et al.  A similarity-based method for genome-wide prediction of disease-relevant human genes , 2002, ECCB.