title: Identifying novel sequence variants of RNA 3D motifs.
abstract: Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non-Watson-Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download.
authors.affiliation: Department of Mathematics and Statistics, Bowling Green State University, Bowling Green, OH 43403, USA zirbel@bgsu.edu.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Zirbel
authors.affiliation: Department of Mathematics and Statistics, Bowling Green State University, Bowling Green, OH 43403, USA.
authors.forename: James
authors.initials: J
authors.lastname: Roll
authors.affiliation: Department of Biology, Bowling Green State University, Bowling Green, OH 43403, USA.
authors.forename: Blake A
authors.initials: BA
authors.lastname: Sweeney
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
authors.forename: Anton I
authors.identifier: http://orcid.org/0000-0001-7279-2682
authors.initials: AI
authors.lastname: Petrov
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Meg
authors.initials: M
authors.lastname: Pirrung
authors.affiliation: Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA.
authors.forename: Neocles B
authors.initials: NB
authors.lastname: Leontis
mesh_terms: D001483:Base Sequence; D014644:Genetic Variation; D008390:Markov Chains; D015233:Models, Statistical; D059372:Nucleotide Motifs; D012313:RNA / Q000737:chemistry*; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software
chemical_list: D012313:RNA