title: Efficient use of accessibility in microRNA target prediction.
abstract: Considering accessibility of the 3'UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by the sum of the opening and hybridization energies, used in currently available algorithms, is not an efficient way to rank predictions. Instead, we describe an algorithm which also considers only the accessible binding sites but which ranks predictions according to over-representation. When compared with experimentally validated and refuted targets in the fruit fly and human, our algorithm shows a remarkable improvement in precision while significantly reducing the computational cost in comparison with other free energy based methods. In the human genome, our algorithm has at least twice higher precision than other methods with their default parameters. In the fruit fly, we find five times more validated targets among the top 500 predictions than other methods with their default parameters. Furthermore, using a common statistical framework we demonstrate explicitly the advantages of using the canonical ensemble instead of using the minimum free energy structure alone. We also find that 'naïve' global folding sometimes outperforms the local folding approach.
authors.affiliation: Laboratory of Theoretical Physical Chemistry, Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Ray M
authors.initials: RM
authors.lastname: Marín
authors.forename: Jirí
authors.initials: J
authors.lastname: Vanícek
mesh_terms: D020413:3' Untranslated Regions; D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D003627:Data Interpretation, Statistical; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
references.citation: Biochem Soc Trans. 2008 Dec;36(Pt 6):1216-9
references.pmid: 19021528
references.citation: Cell. 2007 Apr 20;129(2):303-17
references.pmid: 17397913
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15557-62
references.pmid: 16230613
references.citation: Mol Cell. 2004 Jun 18;14(6):787-99
references.pmid: 15200956
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
references.pmid: 14681465
references.citation: Nat Struct Mol Biol. 2006 Sep;13(9):849-51
references.pmid: 16921378
references.citation: BMC Bioinformatics. 2004 Aug 05;5:105
references.pmid: 15296519
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D140-4
references.pmid: 16381832
references.citation: PLoS Biol. 2003 Dec;1(3):E60
references.pmid: 14691535
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: Nat Struct Mol Biol. 2007 Apr;14(4):287-94
references.pmid: 17401373
references.citation: Nat Methods. 2008 Sep;5(9):813-9
references.pmid: 19160516
references.citation: Bioinformatics. 2009 Dec 1;25(23):3049-55
references.pmid: 19789267
references.citation: BMC Bioinformatics. 2009 Sep 18;10:295
references.pmid: 19765283
references.citation: RNA. 2004 Oct;10(10):1507-17
references.pmid: 15383676
references.citation: Nat Genet. 2009 Jan;41(1):130-4
references.pmid: 19098914
references.citation: Mol Cell. 2007 Jul 6;27(1):91-105
references.pmid: 17612493
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5453-8
references.pmid: 18378902
references.citation: Nat Genet. 2007 Oct;39(10):1278-84
references.pmid: 17893677
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4006-9
references.pmid: 15738385
references.citation: Genome Biol. 2004;5(9):115
references.pmid: 15345038
references.citation: Nat Biotechnol. 2008 May;26(5):578-83
references.pmid: 18438400
references.citation: Bioinformatics. 2006 May 15;22(10):1177-82
references.pmid: 16446276
references.citation: Nature. 2008 Sep 4;455(7209):58-63
references.pmid: 18668040
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D690-7
references.pmid: 19033362
references.citation: Bioinformatics. 2006 Mar 1;22(5):614-5
references.pmid: 16368769
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Nat Rev Genet. 2008 Feb;9(2):102-14
references.pmid: 18197166
references.citation: Bioinformatics. 2008 Dec 15;24(24):2849-56
references.pmid: 18940824
references.citation: PLoS Biol. 2005 Mar;3(3):e85
references.pmid: 15723116
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Nucleic Acids Res. 2009 May;37(8):2419-33
references.pmid: 19295136
references.citation: Bioinformatics. 2008 Nov 15;24(22):2657-63
references.pmid: 18434344
references.citation: Nature. 2009 Jan 22;457(7228):405-12
references.pmid: 19158786
references.citation: Nat Biotechnol. 2008 Aug;26(8):941-6
references.pmid: 18542052
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D105-10
references.pmid: 18996891
references.citation: PLoS Comput Biol. 2005 Dec;1(7):e69
references.pmid: 16355253
references.citation: Genome Biol. 2003;5(1):R1
references.pmid: 14709173
references.citation: BMC Bioinformatics. 2007 Mar 01;8:69
references.pmid: 17331257