miRGator: an integrated system for functional annotation of microRNAs

MicroRNAs (miRNAs) constitute an important class of regulators that are involved in various cellular and disease processes. However, the functional significance of each miRNA is mostly unknown due to the difficulty in identifying target genes and the lack of genome-wide expression data combining miRNAs, mRNAs and proteins. We introduce a novel database, miRGator, that integrates the target prediction, functional analysis, gene expression data and genome annotation. MiRNA function is inferred from the list of target genes predicted by miRanda, PicTar and TargetScanS programs. Statistical enrichment test of target genes in each term is performed for gene ontology, pathway and disease annotations. Associated terms may provide valuable insights for the function of each miRNA. For the expression analysis, miRGator integrates public expression data of miRNA with those of mRNA and protein. Expression correlation between miRNA and target mRNA/proteins is evaluated and their expression patterns can be readily compared. Our web implementation supports diverse query types including miRNA name, gene symbol, gene ontology, pathway and disease terms. Interfaces for exploring common targets or regulatory miRNAs and for profiling compendium expression data have been developed as well. Currently, miRGator, available at: http://genome.ewha.ac.kr/miRGator/, supports the human and mouse genomes.

[1]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[2]  Anton J. Enright,et al.  Requirement of bic/microRNA-155 for Normal Immune Function , 2007, Science.

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

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

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

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

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

[8]  Alex E. Lash,et al.  Gene Expression Omnibus: NCBI gene expression and hybridization array data repository , 2002, Nucleic Acids Res..

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

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

[11]  B. Frey,et al.  The functional landscape of mouse gene expression , 2004, Journal of biology.

[12]  T. Nilsen,et al.  Mechanisms of microRNA‐mediated gene regulation , 2007, Trends in genetics : TIG.

[13]  Emily Dimmer,et al.  The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology , 2004, Nucleic Acids Res..

[14]  Michelle S. Scott,et al.  Global Survey of Organ and Organelle Protein Expression in Mouse: Combined Proteomic and Transcriptomic Profiling , 2006, Cell.

[15]  Susumu Goto,et al.  The KEGG resource for deciphering the genome , 2004, Nucleic Acids Res..

[16]  Ting Wang,et al.  The UCSC Genome Browser Database: update 2009 , 2008, Nucleic Acids Res..

[17]  N. Rajewsky microRNA target predictions in animals , 2006, Nature Genetics.

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

[19]  Gene Ontology Consortium The Gene Ontology (GO) database and informatics resource , 2003 .

[20]  T. Poggio,et al.  Multiclass cancer diagnosis using tumor gene expression signatures , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[22]  David Haussler,et al.  The UCSC genome browser database: update 2007 , 2006, Nucleic Acids Res..

[23]  Steven C. Lawlor,et al.  GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways , 2002, Nature Genetics.

[24]  Jihoon Kim,et al.  ArrayXPath II: mapping and visualizing microarray gene-expression data with biomedical ontologies and integrated biological pathway resources using Scalable Vector Graphics , 2005, Nucleic Acids Res..

[25]  Quaid Morris,et al.  Probing microRNAs with microarrays: tissue specificity and functional inference. , 2004, RNA.

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

[27]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

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

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

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