RNA 3D Modules in Genome-Wide Predictions of RNA 2D Structure.
Recent experimental and computational progress has revealed a large potential for RNA structure in the genome. This has been driven by computational strategies that exploit multiple genomes of related organisms to identify common sequences and secondary structures. However, these computational approaches have two main challenges: they are computationally expensive and they have a relatively high false discovery rate (FDR). Simultaneously, RNA 3D structure analysis has revealed modules composed of non-canonical base pairs which occur in non-homologous positions, apparently by independent evolution. These modules can, for example, occur inside structural elements which in RNA 2D predictions appear as internal loops. Hence one question is if the use of such RNA 3D information can improve the prediction accuracy of RNA secondary structure at a genome-wide level. Here, we use RNAz in combination with 3D module prediction tools and apply them on a 13-way vertebrate sequence-based alignment. We find that RNA 3D modules predicted by metaRNAmodules and JAR3D are significantly enriched in the screened windows compared to their shuffled counterparts. The initially estimated FDR of 47.0% is lowered to below 25% when certain 3D module predictions are present in the window of the 2D prediction. We discuss the implications and prospects for further development of computational strategies for detection of RNA 2D structure in genomic sequence.
Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark; Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Science, University of Copenhagen, Frederiksberg, Denmark.
Corinna
C
Theis
Department of Mathematics and Statistics, Bowling Green State University, Bowling Green, Ohio, United States of America.
Craig L
CL
Zirbel
Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria; Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany; Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany.
Christian Höner
CH
Zu Siederdissen
Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark.
Christian
C
Anthon
Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark; Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria; Research Group Bioinformatics and Computational Biology, University of Vienna, Vienna, Austria.
Ivo L
IL
Hofacker
Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark; Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Henrik
H
Nielsen
Center for non-coding RNA in Technology and Health, University of Copenhagen, Frederiksberg, Denmark; Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Science, University of Copenhagen, Frederiksberg, Denmark.
Jan
J
Gorodkin
D000465:Algorithms; D000818:Animals; D020029:Base Pairing; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
D012313:RNA