title: SimulFold: simultaneously inferring RNA structures including pseudoknots, alignments, and trees using a Bayesian MCMC framework.
abstract: Computational methods for predicting evolutionarily conserved rather than thermodynamic RNA structures have recently attracted increased interest. These methods are indispensable not only for elucidating the regulatory roles of known RNA transcripts, but also for predicting RNA genes. It has been notoriously difficult to devise them to make the best use of the available data and to predict high-quality RNA structures that may also contain pseudoknots. We introduce a novel theoretical framework for co-estimating an RNA secondary structure including pseudoknots, a multiple sequence alignment, and an evolutionary tree, given several RNA input sequences. We also present an implementation of the framework in a new computer program, called SimulFold, which employs a Bayesian Markov chain Monte Carlo method to sample from the joint posterior distribution of RNA structures, alignments, and trees. We use the new framework to predict RNA structures, and comprehensively evaluate the quality of our predictions by comparing our results to those of several other programs. We also present preliminary data that show SimulFold's potential as an alignment and phylogeny prediction method. SimulFold overcomes many conceptual limitations that current RNA structure prediction methods face, introduces several new theoretical techniques, and generates high-quality predictions of conserved RNA structures that may include pseudoknots. It is thus likely to have a strong impact, both on the field of RNA structure prediction and on a wide range of data analyses.
authors: UBC Bioinformatics Centre, University of British Columbia, Vancouver, British Columbia, Canada. irmtraud.meyer@cantab.net
authors: Irmtraud M
authors: IM
authors: Meyer
authors: István
authors: I
authors: Miklós
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001483:Base Sequence; D001499:Bayes Theorem; D003198:Computer Simulation; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010363:Pattern Recognition, Automated; D012313:RNA / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D016415:Sequence Alignment / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D012313:RNA
references: Bioinformatics. 2004 Jan 1;20(1):58-66
references: 14693809
references: Bull Math Biol. 1999 May;61(3):437-67
references: 17883226
references: Nucleic Acids Res. 2004 Sep 24;32(16):4925-36
references: 15448187
references: Nucleic Acids Res. 2003 Jul 1;31(13):3497-500
references: 12824352
references: J Mol Biol. 1999 May 21;288(5):911-40
references: 10329189
references: J Comput Biol. 1998 Fall;5(3):517-30
references: 9773347
references: BMC Bioinformatics. 2005 Mar 24;6:73
references: 15790387
references: BMC Bioinformatics. 2006 Sep 04;7:400
references: 16952317
references: IEEE/ACM Trans Comput Biol Bioinform. 2004 Apr-Jun;1(2):66-77
references: 17048382
references: BMC Bioinformatics. 2004 Oct 26;5:166
references: 15507142
references: Nucleic Acids Res. 1981 Oct 10;9(19):5109-24
references: 6171773
references: J Mol Biol. 1980 Jun 5;139(4):601-25
references: 6997498
references: Bioinformatics. 1999 Jun;15(6):446-54
references: 10383470
references: Nucleic Acids Res. 2005 Apr 28;33(8):2433-9
references: 15860779
references: J Mol Evol. 1981;17(6):368-76
references: 7288891
references: BMC Bioinformatics. 2004 Sep 30;5:140
references: 15458580
references: Bioinformatics. 2005 Mar;21(6):817-20
references: 15479709
references: Bioinformatics. 2005 May 15;21(10):2246-53
references: 15731207
references: J Mol Biol. 2002 Mar 22;317(2):191-203
references: 11902836
references: Nucleic Acids Res. 1994 Jun 11;22(11):2079-88
references: 8029015
references: Mol Biol Evol. 2006 Feb;23(2):254-67
references: 16221896
references: BMC Bioinformatics. 2005 Apr 01;6:83
references: 15804354
references: BMC Mol Biol. 2004 Aug 06;5:10
references: 15298702
references: BMC Bioinformatics. 2005 Apr 08;6:92
references: 15819989
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6515-20
references: 10823910
references: Bioinformatics. 2004 Jul 10;20(10):1591-602
references: 14962926
references: J Mol Biol. 1995 Jun 30;250(1):37-51
references: 7541471
references: Pac Symp Biocomput. 2002;:163-74
references: 11928472
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W142-5
references: 15215367
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15310-5
references: 14676318
references: Proc IEEE Comput Soc Bioinform Conf. 2003;2:159-68
references: 16452790
references: Nucleic Acids Res. 2003 Jul 1;31(13):3429-31
references: 12824340
references: Nucleic Acids Res. 1981 Jan 10;9(1):133-48
references: 6163133
references: Bioinformatics. 2005 May 1;21(9):1815-24
references: 15657094
references: PLoS Biol. 2005 Jun;3(6):e213
references: 15941360
references: Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
references: 12824337
references: Nucleic Acids Res. 1991 May 11;19(9):2489-94
references: 1710358
references: Mol Biol Evol. 2004 Oct;21(10):1913-22
references: 15229291
references: Bioinformatics. 1998;14(8):691-9
references: 9789095
references: Bioinformatics. 2000 Apr;16(4):334-40
references: 10869031
references: J Comput Biol. 2000;7(3-4):409-27
references: 11108471
references: Nature. 1971 Apr 9;230(5293):362-7
references: 4927725
references: Bioinformatics. 2003 Aug 12;19(12):1572-4
references: 12912839
references: Nat New Biol. 1973 Nov 14;246(150):40-1
references: 4519026
references: Genetics. 2002 Jul;161(3):1307-20
references: 12136032
references: Comput Appl Biosci. 1994 Jul;10(4):389-99
references: 7528630
references: Bioinformatics. 2003 Jan;19(1):108-16
references: 12499300
references: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10557-62
references: 16000407
references: Biopolymers. 1993 Sep;33(9):1389-404
references: 7691201
references: Proc Natl Acad Sci U S A. 1980 Nov;77(11):6309-13
references: 6161375
references: BMC Bioinformatics. 2004 Aug 04;5:104
references: 15294028
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W650-3
references: 15980555
references: J Comput Chem. 2003 Oct;24(13):1664-77
references: 12926009
references: IEEE/ACM Trans Comput Biol Bioinform. 2004 Jan-Mar;1(1):53-62
references: 17048408
references: J Mol Biol. 1999 Feb 5;285(5):2053-68
references: 9925784
references: Biopolymers. 1999 Feb;49(2):145-65
references: 10070264
references: J Mol Biol. 2002 Jun 21;319(5):1059-66
references: 12079347
references: Bioinformatics. 2003;19 Suppl 1:i66-73
references: 12855439
references: Nucleic Acids Res. 2003 Jul 1;31(13):3423-8
references: 12824339