Home LiteratureArticle Details
PMID: 25618847 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Detecting riboSNitches with RNA folding algorithms: a genome-wide benchmark.

Nucleic acids research ·Vol. 43 ·No. 3 ·2015-02-18 ·Pages 1859-68

Corley M, Solem A, Qu K, Chang HY, Laederach A

Abstract

Ribonucleic acid (RNA) secondary structure prediction continues to be a significant challenge, in particular when attempting to model sequences with less rigidly defined structures, such as messenger and non-coding RNAs. Crucial to interpreting RNA structures as they pertain to individual phenotypes is the ability to detect RNAs with large structural disparities caused by a single nucleotide variant (SNV) or riboSNitches. A recently published human genome-wide parallel analysis of RNA structure (PARS) study identified a large number of riboSNitches as well as non-riboSNitches, providing an unprecedented set of RNA sequences against which to benchmark structure prediction algorithms. Here we evaluate 11 different RNA folding algorithms' riboSNitch prediction performance on these data. We find that recent algorithms designed specifically to predict the effects of SNVs on RNA structure, in particular remuRNA, RNAsnp and SNPfold, perform best on the most rigorously validated subsets of the benchmark data. In addition, our benchmark indicates that general structure prediction algorithms (e.g. RNAfold and RNAstructure) have overall better performance if base pairing probabilities are considered rather than minimum free energy calculations. Although overall aggregate algorithmic performance on the full set of riboSNitches is relatively low, significant improvement is possible if the highest confidence predictions are evaluated independently.

MeSH Terms
Algorithms Genome, Human Humans Nucleic Acid Conformation RNA/chemistry
Chemicals
RNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Corley Meredith
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 37599, USA Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Solem Amanda
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 37599, USA.
Qu Kun
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Chang Howard Y
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Laederach Alain
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 37599, USA Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA alain@unc.edu.
References (74)
74 references, click to expand
  1. RNA flexibility in the dimerization domain of a gamma retrovirus.
    Nat Chem Biol. 2005 Jul;1(2):104-11 PMID: 16408007
  2. Landscape and variation of RNA secondary structure across the human transcriptome.
    Nature. 2014 Jan 30;505(7485):706-9 PMID: 24476892
  3. Non-coding RNAs: regulators of disease.
    J Pathol. 2010 Jan;220(2):126-39 PMID: 19882673
  4. Mutation of the 5'-untranslated region stem-loop structure inhibits α1(I) collagen expression in vivo.
    J Biol Chem. 2011 Mar 11;286(10):8609-19 PMID: 21193410
  5. Efficient sampling of RNA secondary structures from the Boltzmann ensemble of low-energy: the boustrophedon method.
    J Math Biol. 2008 Jan;56(1-2):107-27 PMID: 17932676
  6. RNA and protein folding: common themes and variations.
    Biochemistry. 2005 Apr 5;44(13):4957-70 PMID: 15794634
  7. Intracellular folding of the Tetrahymena group I intron depends on exon sequence and promoter choice.
    RNA. 2004 Oct;10(10):1526-32 PMID: 15337845
  8. Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo.
    Nature. 2014 Jan 30;505(7485):701-5 PMID: 24336214
  9. Efficient algorithms for probing the RNA mutation landscape.
    PLoS Comput Biol. 2008;4(8):e1000124 PMID: 18688270
  10. Site identification in high-throughput RNA-protein interaction data.
    Bioinformatics. 2012 Dec 1;28(23):3013-20 PMID: 23024010
  11. RNAmute: RNA secondary structure mutation analysis tool.
    BMC Bioinformatics. 2006;7:221 PMID: 16638137
  12. RNASTAR: an RNA STructural Alignment Repository that provides insight into the evolution of natural and artificial RNAs.
    RNA. 2012 Jul;18(7):1319-27 PMID: 22645380
  13. Genome-wide measurement of RNA folding energies.
    Mol Cell. 2012 Oct 26;48(2):169-81 PMID: 22981864
  14. A comprehensive comparison of comparative RNA structure prediction approaches.
    BMC Bioinformatics. 2004 Sep 30;5:140 PMID: 15458580
  15. RNA folding in living cells.
    RNA Biol. 2010 Nov-Dec;7(6):634-41 PMID: 21045541
  16. ROC analysis: applications to the classification of biological sequences and 3D structures.
    Brief Bioinform. 2008 May;9(3):198-209 PMID: 18192302
  17. CONTRAfold: RNA secondary structure prediction without physics-based models.
    Bioinformatics. 2006 Jul 15;22(14):e90-8 PMID: 16873527
  18. ViennaRNA Package 2.0.
    Algorithms Mol Biol. 2011 Nov 24;6:26 PMID: 22115189
  19. Slow formation of a pseudoknot structure is rate limiting in the productive co-transcriptional folding of the self-splicing Candida intron.
    RNA. 2009 Nov;15(11):1986-92 PMID: 19710184
  20. Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies.
    Nucleic Acids Res. 2013 Jan 7;41(1):44-53 PMID: 23125360
  21. From consensus structure prediction to RNA gene finding.
    Brief Funct Genomic Proteomic. 2009 Nov;8(6):461-71 PMID: 19833701
  22. Beyond Mfold: recent advances in RNA bioinformatics.
    J Biotechnol. 2006 Jun 25;124(1):41-55 PMID: 16530285
  23. Computing the partition function and sampling for saturated secondary structures of RNA, with respect to the Turner energy model.
    J Comput Biol. 2007 Mar;14(2):190-215 PMID: 17456015
  24. RNAstructure: software for RNA secondary structure prediction and analysis.
    BMC Bioinformatics. 2010;11:129 PMID: 20230624
  25. A mechanistic framework for co-transcriptional folding of the HDV genomic ribozyme in the presence of downstream sequence.
    J Mol Biol. 2002 Nov 15;324(1):1-16 PMID: 12421555
  26. On the importance of cotranscriptional RNA structure formation.
    RNA. 2013 Nov;19(11):1461-73 PMID: 24131802
  27. Alu elements shape the primate transcriptome by cis-regulation of RNA editing.
    Genome Biol. 2014;15(2):R28 PMID: 24485196
  28. The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data.
    Nature. 2008 Mar 6;452(7183):51-5 PMID: 18322526
  29. Recent insights on RNA folding mechanisms from catalytic RNA.
    Cell Mol Life Sci. 2000 May;57(5):796-808 PMID: 10892344
  30. Structural effects of linkage disequilibrium on the transcriptome.
    RNA. 2012 Jan;18(1):77-87 PMID: 22109839
  31. An efficient method for the prediction of deleterious multiple-point mutations in the secondary structure of RNAs using suboptimal folding solutions.
    BMC Bioinformatics. 2008;9:222 PMID: 18445289
  32. RNA structure determination using nuclease digestion.
    Cold Spring Harb Protoc. 2013 Apr;2013(4):379-82 PMID: 23547152
  33. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs.
    Biochemistry. 1998 Oct 20;37(42):14719-35 PMID: 9778347
  34. The Azoarcus group I intron ribozyme misfolds and is accelerated for refolding by ATP-dependent RNA chaperone proteins.
    J Biol Chem. 2011 Oct 28;286(43):37304-12 PMID: 21878649
  35. Prediction of RNA secondary structure using generalized centroid estimators.
    Bioinformatics. 2009 Feb 15;25(4):465-73 PMID: 19095700
  36. The RNAsnp web server: predicting SNP effects on local RNA secondary structure.
    Nucleic Acids Res. 2013 Jul;41(Web Server issue):W475-9 PMID: 23630321
  37. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing.
    Nat Methods. 2010 Dec;7(12):995-1001 PMID: 21057495
  38. Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
    PLoS One. 2014;9(2):e85041 PMID: 24586236
  39. Structural studies of RNase P.
    Annu Rev Biophys. 2013;42:537-57 PMID: 23654306
  40. RNA multi-structure landscapes. A study based on temperature dependent partition functions.
    Eur Biophys J. 1993;22(1):13-24 PMID: 7685689
  41. The equilibrium partition function and base pair binding probabilities for RNA secondary structure.
    Biopolymers. 1990 May-Jun;29(6-7):1105-19 PMID: 1695107
  42. Mod-seq: high-throughput sequencing for chemical probing of RNA structure.
    RNA. 2014 May;20(5):713-20 PMID: 24664469
  43. Molecular biology: A second layer of information in RNA.
    Nature. 2014 Jan 30;505(7485):621-2 PMID: 24476882
  44. pROC: an open-source package for R and S+ to analyze and compare ROC curves.
    BMC Bioinformatics. 2011;12:77 PMID: 21414208
  45. UNAFold: software for nucleic acid folding and hybridization.
    Methods Mol Biol. 2008;453:3-31 PMID: 18712296
  46. On finding all suboptimal foldings of an RNA molecule.
    Science. 1989 Apr 7;244(4900):48-52 PMID: 2468181
  47. Disease-associated mutations that alter the RNA structural ensemble.
    PLoS Genet. 2010 Aug;6(8):e1001074 PMID: 20808897
  48. MoD Tools: regulatory motif discovery in nucleotide sequences from co-regulated or homologous genes.
    Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W566-70 PMID: 16845071
  49. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.
    PLoS Biol. 2008 Apr 29;6(4):e96 PMID: 18447581
  50. Evaluating our ability to predict the structural disruption of RNA by SNPs.
    BMC Genomics. 2012;13 Suppl 4:S6 PMID: 22759654
  51. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.
    Biometrics. 1988 Sep;44(3):837-45 PMID: 3203132
  52. RNA: riboSNitches reveal heredity in RNA secondary structure.
    Nat Rev Genet. 2014 Apr;15(4):219 PMID: 24535248
  53. Understanding the role of three-dimensional topology in determining the folding intermediates of group I introns.
    Biophys J. 2013 Mar 19;104(6):1326-37 PMID: 23528092
  54. Stability and cooperativity of individual tertiary contacts in RNA revealed through chemical denaturation.
    Nat Struct Biol. 2000 May;7(5):371-4 PMID: 10802732
  55. Meeting report of the RNA Ontology Consortium January 8-9, 2011.
    Stand Genomic Sci. 2011 Apr 29;4(2):252-6 PMID: 21677862
  56. Evaluation of the information content of RNA structure mapping data for secondary structure prediction.
    RNA. 2010 Jun;16(6):1108-17 PMID: 20413617
  57. RNA structure prediction: an overview of methods.
    Methods Mol Biol. 2012;905:99-122 PMID: 22736001
  58. NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure.
    Nucleic Acids Res. 2010 Jan;38(Database issue):D280-2 PMID: 19880381
  59. Structure of transfer RNAs: similarity and variability.
    Wiley Interdiscip Rev RNA. 2012 Jan-Feb;3(1):37-61 PMID: 21957054
  60. A heterozygous variant in the human cardiac miR-133 gene, MIR133A2, alters miRNA duplex processing and strand abundance.
    BMC Genet. 2013;14:18 PMID: 23497314
  61. Partition function and base pairing probabilities of RNA heterodimers.
    Algorithms Mol Biol. 2006 Mar 16;1(1):3 PMID: 16722605
  62. RNAcontext: a new method for learning the sequence and structure binding preferences of RNA-binding proteins.
    PLoS Comput Biol. 2010;6:e1000832 PMID: 20617199
  63. Measuring the thermodynamics of RNA secondary structure formation.
    Biopolymers. 1997;44(3):309-19 PMID: 9591481
  64. Endonucleolytic cleavage of eukaryotic mRNAs with stalls in translation elongation.
    Nature. 2006 Mar 23;440(7083):561-4 PMID: 16554824
  65. RNAz 2.0: improved noncoding RNA detection.
    Pac Symp Biocomput. 2010;:69-79 PMID: 19908359
  66. Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast.
    RNA. 2006 Dec;12(12):2149-59 PMID: 17135489
  67. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure.
    J Mol Biol. 1999 May 21;288(5):911-40 PMID: 10329189
  68. Structure of an RNA switch that enforces stringent retroviral genomic RNA dimerization.
    Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13640-5 PMID: 16945907
  69. Strategies for RNA folding and assembly.
    Nat Rev Mol Cell Biol. 2004 Nov;5(11):908-19 PMID: 15520810
  70. Genome-wide measurement of RNA secondary structure in yeast.
    Nature. 2010 Sep 2;467(7311):103-7 PMID: 20811459
  71. Mutational spectrum of delta-globin gene in the Portuguese population.
    Eur J Haematol. 2007 Nov;79(5):422-8 PMID: 17916081
  72. Coupling pre-mRNA processing to transcription on the RNA factory assembly line.
    RNA Biol. 2013 Mar;10(3):380-90 PMID: 23392244
  73. Clinical assessment incorporating a personal genome.
    Lancet. 2010 May 1;375(9725):1525-35 PMID: 20435227
  74. In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features.
    Nature. 2014 Jan 30;505(7485):696-700 PMID: 24270811
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkv010
Email
alain@unc.edu
Published
2015-02-18
Epub
2015-00-23
Pages
1859-68
Language
English
Region
England
NLM ID
0411011
PMCID
PMC4330374
Subset
IM
Grants
NHGRI NIH HHS · R01 HG004361 · United States
NHLBI NIH HHS · R01 HL111527 · United States
NHGRI NIH HHS · HG004361 · United States
NIGMS NIH HHS · R01 GM101237 · United States
NIGMS NIH HHS · GM101237 · United States
NHLBI NIH HHS · HL111527 · United States
External Links
PubMed source DOI: 10.1093/nar/gkv010 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2