Functional homogeneity in microRNA target heterogeneity--a new sight into human microRNomics.

MicroRNomics is a novel genomics that studies the identification, targets, biological functions, etc., of microRNAs (miRNAs) on a genomic scale. Computational target prediction algorithms are important applications in microRNomics. However, the overlaps between target sets predicted by different algorithms for one miRNA are often small. Our work is initiated to find the reasons causing "heterogeneity" and investigate whether the heterogeneous targets are homogeneous on functional levels by integrating similarity metrics. The results suggest that most human miRNAs own heterogeneous targets. The dissimilarity of thermodynamic characteristics and the different treatment of 3'-compensatory sites adopted by algorithms are the main reasons for target "heterogeneity." Meanwhile, we find most miRNA heterogeneous targets are functional homogeneity because of the common principles such as sites conservation and G:U wobble pairs in different algorithms. Our findings reveal the "functional homogeneity in miRNA target heterogeneity." The conclusions provide a perspective of microRNomics on functional levels, which introduce a new sight into human miRNA targets.

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

[2]  Holger Fröhlich,et al.  GOSim – an R-package for computation of information theoretic GO similarities between terms and gene products , 2007, BMC Bioinformatics.

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

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

[5]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[6]  Chunxiang Zhang,et al.  MicroRNomics: a newly emerging approach for disease biology. , 2008, Physiological genomics.

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

[8]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

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

[10]  R. Kandpal,et al.  The era of 'omics unlimited. , 2009, BioTechniques.

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

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

[13]  Bibekanand Mallick,et al.  miRNomics-The bioinformatics of microRNA genes. , 2007, Biochemical and biophysical research communications.

[14]  Wen-Hsiung Li,et al.  MicroRNA regulation of human protein protein interaction network. , 2007, RNA.

[15]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

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

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

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

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

[20]  Achuthsankar S. Nair,et al.  MTar: a computational microRNA target prediction architecture for human transcriptome , 2010, BMC Bioinformatics.

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

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

[23]  Brad T. Sherman,et al.  DAVID: Database for Annotation, Visualization, and Integrated Discovery , 2003, Genome Biology.

[24]  James R. Brown,et al.  A computational view of microRNAs and their targets. , 2005, Drug discovery today.

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

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

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

[28]  Isaac Bentwich Prediction and validation of microRNAs and their targets , 2005, FEBS letters.

[29]  Dekang Lin,et al.  An Information-Theoretic Definition of Similarity , 1998, ICML.

[30]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

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

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

[33]  Yuriy Gusev,et al.  Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. , 2007, RNA.

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

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

[36]  C. Spillane,et al.  Prediction and validation of microRNA targets in animal genomes , 2007, Journal of Biosciences.