Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites

AbstractmirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.

[1]  C. Coulson,et al.  Molecular Architecture , 1953, Nature.

[2]  E. Lai.  Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

[3]  Anton J. Enright,et al.  MicroRNA Targets in Drosophila , 2003, Genome Biology.

[4]  Bernhard Schölkopf,et al.  A tutorial on support vector regression , 2004, Stat. Comput..

[5]  Eun-Young Choi,et al.  The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR. , 2004, Genes & development.

[6]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

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

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

[9]  D. Haussler,et al.  Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. , 2005, Genome research.

[10]  Ligang Wu,et al.  Micro-RNA Regulation of the Mammalian lin-28 Gene during Neuronal Differentiation of Embryonal Carcinoma Cells , 2005, Molecular and Cellular Biology.

[11]  Jan Krüger,et al.  RNAhybrid: microRNA target prediction easy, fast and flexible , 2006, Nucleic Acids Res..

[12]  Oliver Hobert,et al.  Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions , 2006, Nature Structural &Molecular Biology.

[13]  Colin N. Dewey,et al.  A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans , 2006, Current Biology.

[14]  L. Lim,et al.  Transcripts Targeted by the MicroRNA-16 Family Cooperatively Regulate Cell Cycle Progression , 2007, Molecular and Cellular Biology.

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

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

[17]  Reuven Agami,et al.  RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA , 2007, Cell.

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

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

[20]  Daniel Herschlag,et al.  Systematic Identification of mRNAs Recruited to Argonaute 2 by Specific microRNAs and Corresponding Changes in Transcript Abundance , 2008, PloS one.

[21]  Oliver Hobert,et al.  Molecular architecture of a miRNA-regulated 3' UTR. , 2008, RNA.

[22]  Stefan L Ameres,et al.  The impact of target site accessibility on the design of effective siRNAs , 2008, Nature Biotechnology.

[23]  A. Silahtaroglu,et al.  Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver , 2007, Nucleic acids research.

[24]  M. Zavolan,et al.  Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. , 2008, RNA.

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

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

[27]  S. Kauppinen,et al.  LNA-mediated microRNA silencing in non-human primates , 2008, Nature.

[28]  Dang D. Long,et al.  mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein–enriched transcripts , 2008, Nature Methods.

[29]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[30]  T. Wurdinger,et al.  MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators , 2008, Molecular and Cellular Biology.

[31]  Mihaela Zavolan,et al.  Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets. , 2009, Genome research.

[32]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

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

[34]  Nectarios Koziris,et al.  Accurate microRNA target prediction correlates with protein repression levels , 2009, BMC Bioinformatics.

[35]  Martin L. Miller,et al.  Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs , 2009, Nature Biotechnology.

[36]  Oliver Hofmann,et al.  miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. , 2009, Molecular cell.

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

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

[39]  Anders Krogh,et al.  Signatures of RNA binding proteins globally coupled to effective microRNA target sites. , 2010, Genome research.