New algorithms to represent complex pseudoknotted RNA structures in dot-bracket notation

Abstract

MotivationUnderstanding the formation, architecture and roles of pseudoknots in RNA structures are one of the most difficult challenges in RNA computational biology and structural bioinformatics. Methods predicting pseudoknots typically perform this with poor accuracy, often despite experimental data incorporation. Existing bioinformatic approaches differ in terms of pseudoknots’ recognition and revealing their nature. A few ways of pseudoknot classification exist, most common ones refer to a genus or order. Following the latter one, we propose new algorithms that identify pseudoknots in RNA structure provided in BPSEQ format, determine their order and encode in dot-bracket-letter notation. The proposed encoding aims to illustrate the hierarchy of RNA folding.ResultsNew algorithms are based on dynamic programming and hybrid (combining exhaustive search and random walk) approaches. They evolved from elementary algorithm implemented within the workflow of RNA FRABASE 1.0, our database of RNA structure fragments. They use different scoring functions to rank dissimilar dot-bracket representations of RNA structure. Computational experiments show an advantage of new methods over the others, especially for large RNA structures.Availability and implementationPresented algorithms have been implemented as new functionality of RNApdbee webserver and are ready to use at http://rnapdbee.cs.put.poznan.pl.Supplementary information Supplementary data are available at Bioinformatics online.

RNAfitme: a webserver for modeling nucleobase and nucleoside residue conformation in fixed-backbone RNA structures

“…It will help in broadening the range of possible 3D structure modifications and introduce more flexibility into the remodeling process. Such a change can improve the accuracy of predicting the pseudoknotted RNA structures which currently constitute quite a significant problem of computational prediction methods [ 51 ]. Future plans include also implementation of procedures to support modified residues in the input RNA structure.…”

RNApdbee 2.0: multifunctional tool for RNA structure annotation

“…The user can also decide how to treat non-canonical and isolated base pairs which strongly impact pseudoknot orders and structure topology. The second step has been recently introduced and has five algorithms, Hybrid Algorithm (default), Dynamic Programming, Elimination Min-Gain, Elimination Max-Conflicts, First-Come-First-Served ( 16 ), to support high-order pseudoknot processing. They follow different routines to find the optimum nested substructure, identify pseudoknot orders and encode the secondary structure topology in extended dot-bracket notation.…”

RNApolis: Computational Platform for RNA Structure Analysis

“…This paper presents RNApolis, a new computing platform that collects bioinformatics tools developed by the RNA bioinformatics group of researchers affiliated at the Institute of Computing Science, Poznan University of Technology and the Institute of Bioorganic Chemistry, Polish Academy of Sciences. The following RNA-dedicated tools are accessible via the platform: RNA FRABASE [42,43], RNAComposer [4,44,46], RNApdbee [5,59], RNAlyzer [30], RNAssess [31], RNAfitme [5,6,58], and RNAvista [7]. They aim to support the research which focuses on the secondary and the tertiary structure of RNA molecules.…”

“…RNA structure is hierarchical ( Figure 1) [5,14]. This hierarchy allows the architecture and properties of a molecule to be studied from partial knowledge, which is often sufficient to draw basic conclusions [13,35].…”

“…Recently, they have been strengthened by the possibility to incorporate constraints from chemical probing, primarily SHAPE method [20,32,38]. Automated methods of RNA secondary structure annotation are also developing [5,18,48,59]. Both these paths, prediction and annotation, result in a set of different secondary structures obtained for the same RNA molecule.…”