Web resources for microRNA research.

Over the last decade thousands of microRNAs (miRNAs) have been discovered in all kinds of taxa. The ever growing number of identified miRNA genes required ordered cataloging and annotation. This has led to the development of miRNA web resources.MiRNA web resources can be referred to either as web accessible databases (repositories) or web applications that provide a defined computational task upon user request. Today, more than three dozen web accessible resources exist that gather, organize and annotate all kinds of miRNA related data. According to the type of data or data processing method, these miRNA web resources can be classified as miRNA sequence and annotation databases, resources and tools for predicted as well as experimentally validated targets, databases of miRNA regulation and expression, functional annotation and mapping databases and a number of other tools and resources that are species-specific or focus on particular phenotypes.This chapter provides an overview of the different types of miRNA web resources and their purpose and gives some examples for each category. Furthermore, some valuable miRNA web applications will be introduced. Finally, strategies for miRNA data retrieval and associated risks and pitfalls will be discussed.

[1]  Anton J. Enright,et al.  SylArray: a web server for automated detection of miRNA effects from expression data , 2010, Bioinform..

[2]  Dennis B. Troup,et al.  NCBI GEO: archive for functional genomics data sets—10 years on , 2010, Nucleic Acids Res..

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

[4]  Andrew M. Waterhouse,et al.  The FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation , 2009, Genome Biology.

[5]  Nectarios Koziris,et al.  TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support , 2011, Nucleic Acids Res..

[6]  C. Croce Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[7]  Carole A. Goble,et al.  BioCatalogue: a universal catalogue of web services for the life sciences , 2010, Nucleic Acids Res..

[8]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[9]  Nikolaus Rajewsky,et al.  Computational identification of microRNA targets. , 2004 .

[10]  Dong Yue,et al.  Improving performance of mammalian microRNA target prediction , 2010, BMC Bioinformatics.

[11]  Sanghamitra Bandyopadhyay,et al.  PuTmiR: A database for extracting neighboring transcription factors of human microRNAs , 2010, BMC Bioinformatics.

[12]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[13]  D. Welch,et al.  Metastamir: the field of metastasis-regulatory microRNA is spreading. , 2009, Cancer research.

[14]  David J. Arenillas,et al.  The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences , 2008, Nucleic Acids Res..

[15]  Curtis Balch,et al.  MicroRNA and mRNA integrated analysis (MMIA): a web tool for examining biological functions of microRNA expression , 2009, Nucleic Acids Res..

[16]  A. Hatzigeorgiou,et al.  A combined computational-experimental approach predicts human microRNA targets. , 2004, Genes & development.

[17]  A. Hatzigeorgiou,et al.  A guide through present computational approaches for the identification of mammalian microRNA targets , 2006, Nature Methods.

[18]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[19]  Michal Linial,et al.  MiRror: a combinatorial analysis web tool for ensembles of microRNAs and their targets , 2010, Bioinform..

[20]  Sanghyuk Lee,et al.  miRGator v2.0 : an integrated system for functional investigation of microRNAs , 2010, Nucleic Acids Res..

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

[22]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[23]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[24]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[25]  Erich E. Wanker,et al.  UniHI 4: new tools for query, analysis and visualization of the human protein–protein interactome , 2008, Nucleic Acids Res..

[26]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Aebersold,et al.  A quantitative targeted proteomics approach to validate predicted microRNA targets in C. elegans , 2010, Nature Methods.

[28]  A. T. Freitas,et al.  Current tools for the identification of miRNA genes and their targets , 2009, Nucleic acids research.

[29]  L. Lim,et al.  MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression , 2008, Molecular and Cellular Biology.

[30]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

[31]  David J. Arenillas,et al.  MIR@NT@N: a framework integrating transcription factors, microRNAs and their targets to identify sub-network motifs in a meta-regulation network model , 2011, BMC Bioinformatics.

[32]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[33]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[34]  J. Kitzman,et al.  Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. , 2007, RNA.

[35]  R. Russell,et al.  bantam Encodes a Developmentally Regulated microRNA that Controls Cell Proliferation and Regulates the Proapoptotic Gene hid in Drosophila , 2003, Cell.

[36]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[37]  Helen E. Parkinson,et al.  ArrayExpress—a public database of microarray experiments and gene expression profiles , 2006, Nucleic Acids Res..

[38]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[39]  Anders Krogh,et al.  miRMaid: a unified programming interface for microRNA data resources , 2010, BMC Bioinformatics.

[40]  R. Hoffmann A wiki for the life sciences where authorship matters , 2008, Nature Genetics.

[41]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[42]  A. Mele,et al.  Ago HITS-CLIP decodes miRNA-mRNA interaction maps , 2009, Nature.

[43]  Norbert Gretz,et al.  miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes , 2011, J. Biomed. Informatics.

[44]  S. Hammond MicroRNAs as tumor suppressors , 2007, Nature Genetics.

[45]  Antony Le Béchec,et al.  M@IA: A Modular Open-Source Application for Microarray Workflow and Integrative Datamining , 2008, Silico Biol..

[46]  Asaf Levy,et al.  TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates , 2007, Nucleic Acids Res..

[47]  Michael J Kerin,et al.  Circulating microRNAs as Novel Minimally Invasive Biomarkers for Breast Cancer , 2010, Annals of surgery.

[48]  Olaf Wolkenhauer,et al.  Computational analysis of target hub gene repression regulated by multiple and cooperative miRNAs , 2012, Nucleic acids research.

[49]  Jun S. Song,et al.  Chromatin structure analyses identify miRNA promoters , 2008 .

[50]  George A Calin,et al.  MicroRNAs and cancer: Profile, profile, profile , 2007, International journal of cancer.

[51]  Andrew Williams,et al.  Cross-platform analysis of global microRNA expression technologies , 2010, BMC Genomics.

[52]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[53]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[54]  Chi-Ying F. Huang,et al.  miRTarBase: a database curates experimentally validated microRNA–target interactions , 2010, Nucleic Acids Res..

[55]  Changning Liu,et al.  dbDEMC: a database of differentially expressed miRNAs in human cancers , 2010, BMC Genomics.

[56]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[57]  Julius Brennecke,et al.  Identification of Drosophila MicroRNA Targets , 2003, PLoS biology.

[58]  Kiyoshi Asai,et al.  The Functional RNA Database 3.0: databases to support mining and annotation of functional RNAs , 2008, Nucleic Acids Res..

[59]  R. Plasterk,et al.  The diverse functions of microRNAs in animal development and disease. , 2006, Developmental cell.

[60]  A. Hatzigeorgiou,et al.  TarBase: A comprehensive database of experimentally supported animal microRNA targets. , 2005, RNA.

[61]  Angela Gallo,et al.  ADARs: allies or enemies? The importance of A‐to‐I RNA editing in human disease: from cancer to HIV‐1 , 2012, Biological reviews of the Cambridge Philosophical Society.

[62]  Bing Shi,et al.  TAM: A method for enrichment and depletion analysis of a microRNA category in a list of microRNAs , 2010, BMC Bioinformatics.

[63]  Mihaela Zavolan,et al.  Inference of miRNA targets using evolutionary conservation and pathway analysis , 2007, BMC Bioinformatics.

[64]  Angela Re,et al.  CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse , 2010, BMC Bioinformatics.

[65]  W. Ritchie,et al.  Predicting microRNA targets and functions: traps for the unwary , 2009, Nature Methods.

[66]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.

[67]  S. Hammond,et al.  MicroRNAs as oncogenes. , 2006, Current opinion in genetics & development.

[68]  Gabriele Sales,et al.  MAGIA, a web-based tool for miRNA and Genes Integrated Analysis , 2010, Nucleic Acids Res..

[69]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[70]  Yu-Ping Wang,et al.  MiRTif: a support vector machine-based microRNA target interaction filter , 2008, BMC Bioinformatics.

[71]  Boqin Qiang,et al.  Improving the prediction of human microRNA target genes by using ensemble algorithm , 2007, FEBS letters.

[72]  Dennis Shasha,et al.  miRò: a miRNA knowledge base , 2009, Database J. Biol. Databases Curation.

[73]  Xiaowei Wang,et al.  Sequence analysis Prediction of both conserved and nonconserved microRNA targets in animals , 2007 .

[74]  Scott A. Givan,et al.  ASRP: the Arabidopsis Small RNA Project Database , 2004, Nucleic Acids Res..

[75]  Evgeny M. Zdobnov,et al.  miROrtho: computational survey of microRNA genes , 2008, Nucleic Acids Res..

[76]  Martin Reczko,et al.  DIANA-mirPath: Integrating human and mouse microRNAs in pathways , 2009, Bioinform..

[77]  Byoung-Tak Zhang,et al.  miTarget: microRNA target gene prediction using a support vector machine , 2006, BMC Bioinformatics.

[78]  Tongbin Li,et al.  miRecords: an integrated resource for microRNA–target interactions , 2008, Nucleic Acids Res..

[79]  David J. Arenillas,et al.  JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles , 2009, Nucleic Acids Res..

[80]  Paul P. Gardner,et al.  Identification of miRNA targets with stable isotope labeling by amino acids in cell culture , 2006, Nucleic acids research.

[81]  Tzong-Yi Lee,et al.  Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data , 2011, Nucleic acids research.

[82]  Jian Gu,et al.  PI3K signaling and miRNA expression during the response of quiescent human fibroblasts to distinct proliferative stimuli , 2006, Genome Biology.

[83]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[84]  Sanghamitra Bandyopadhyay,et al.  TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples , 2009, Bioinform..

[85]  C. Harris,et al.  Genetic variation in microRNA networks: the implications for cancer research , 2010, Nature Reviews Cancer.

[86]  Hsien-Da Huang,et al.  miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes , 2005, Nucleic Acids Res..

[87]  Christoph Rodak,et al.  MirZ: an integrated microRNA expression atlas and target prediction resource , 2009, Nucleic Acids Res..

[88]  Anton J. Enright,et al.  MicroRNA targets in Drosophila , 2003, Genome Biology.

[89]  N. Rajewsky,et al.  Silencing of microRNAs in vivo with ‘antagomirs’ , 2005, Nature.

[90]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[91]  Xiaowei Wang miRDB: a microRNA target prediction and functional annotation database with a wiki interface. , 2008, RNA.

[92]  Pascal Barbry,et al.  Bioinformatics Applications Note Gene Expression Mirontop: Mining Micrornas Targets across Large Scale Gene Expression Studies , 2022 .

[93]  Yitzhak Pilpel,et al.  Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network , 2007, PLoS Comput. Biol..

[94]  Ming Lu,et al.  TransmiR: a transcription factor–microRNA regulation database , 2009, Nucleic Acids Res..

[95]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

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

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

[98]  T. Barrette,et al.  Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. , 2007, Neoplasia.

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

[100]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[101]  Molly Megraw,et al.  miRGen: a database for the study of animal microRNA genomic organization and function , 2006, Nucleic Acids Res..

[102]  Zhenyu Xuan,et al.  A biochemical approach to identifying microRNA targets , 2007, Proceedings of the National Academy of Sciences.

[103]  C. Croce,et al.  MicroRNA-cancer connection: the beginning of a new tale. , 2006, Cancer research.

[104]  Peter F Stadler,et al.  Molecular evolution of a microRNA cluster. , 2004, Journal of molecular biology.

[105]  Brendan J. Frey,et al.  Bayesian Inference of MicroRNA Targets from Sequence and Expression Data , 2007, J. Comput. Biol..

[106]  Elda Rossi,et al.  Identification of microRNA activity by Targets' Reverse EXpression , 2009, Bioinform..

[107]  Kenta Nakai,et al.  DBTSS provides a tissue specific dynamic view of Transcription Start Sites , 2009, Nucleic Acids Res..

[108]  Edwin Wang,et al.  Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers , 2007, Nucleic acids research.

[109]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[110]  George A. Calin,et al.  UCbase & miRfunc: a database of ultraconserved sequences and microRNA function , 2008, Nucleic Acids Res..

[111]  Anton J. Enright,et al.  Detecting microRNA binding and siRNA off-target effects from expression data , 2008, Nature Methods.

[112]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[113]  Shannan J. Ho Sui,et al.  oPOSSUM: integrated tools for analysis of regulatory motif over-representation , 2007, Nucleic Acids Res..

[114]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[115]  Ola Snøve,et al.  Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms. , 2005, RNA.

[116]  C. Croce,et al.  MicroRNAs in Cancer. , 2009, Annual review of medicine.

[117]  Xiaowei Wang,et al.  Systematic identification of microRNA functions by combining target prediction and expression profiling , 2006, Nucleic acids research.

[118]  F. Slack,et al.  The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. , 2000, Molecular cell.

[119]  Hanah Margalit,et al.  RepTar: a database of predicted cellular targets of host and viral miRNAs , 2010, Nucleic Acids Res..

[120]  Scott B. Dewell,et al.  Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP , 2010, Cell.

[121]  M. Hecker,et al.  Integration of MicroRNA Databases to Study MicroRNAs Associated with Multiple Sclerosis , 2012, Molecular Neurobiology.

[122]  W. Filipowicz,et al.  The widespread regulation of microRNA biogenesis, function and decay , 2010, Nature Reviews Genetics.

[123]  Chiwai Wong,et al.  A computational screen for mouse signaling pathways targeted by microRNA clusters. , 2008, RNA.

[124]  Yvonne Tay,et al.  A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes , 2006, Cell.

[125]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[126]  Thomas Tuschl,et al.  miRNAs in human cancer , 2011, The Journal of pathology.

[127]  Dmitrij Frishman,et al.  TargetSpy: a supervised machine learning approach for microRNA target prediction , 2010, BMC Bioinformatics.

[128]  G. Ruvkun,et al.  A uniform system for microRNA annotation. , 2003, RNA.

[129]  Hui Zhou,et al.  starBase: a database for exploring microRNA–mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data , 2010, Nucleic Acids Res..