The foldalign web server for pairwise structural RNA alignment and mutual motif search

Foldalign is a Sankoff-based algorithm for making structural alignments of RNA sequences. Here, we present a web server for making pairwise alignments between two RNA sequences, using the recently updated version of foldalign. The server can be used to scan two sequences for a common structural RNA motif of limited size, or the entire sequences can be aligned locally or globally. The web server offers a graphical interface, which makes it simple to make alignments and manually browse the results. The web server can be accessed at

Fast Pairwise Structural RNA Alignments by Pruning of the Dynamical Programming Matrix

It has become clear that noncoding RNAs (ncRNA) play important roles in cells, and emerging studies indicate that there might be a large number of unknown ncRNAs in mammalian genomes. There exist computational methods that can be used to search for ncRNAs by comparing sequences from different genomes. One main problem with these methods is their computational complexity, and heuristics are therefore employed. Two heuristics are currently very popular: pre-folding and pre-aligning. However, these heuristics are not ideal, as pre-aligning is dependent on sequence similarity that may not be present and pre-folding ignores the comparative information. Here, pruning of the dynamical programming matrix is presented as an alternative novel heuristic constraint. All subalignments that do not exceed a length-dependent minimum score are discarded as the matrix is filled out, thus giving the advantage of providing the constraints dynamically. This has been included in a new implementation of the FOLDALIGN algorithm for pairwise local or global structural alignment of RNA sequences. It is shown that time and memory requirements are dramatically lowered while overall performance is maintained. Furthermore, a new divide and conquer method is introduced to limit the memory requirement during global alignment and backtrack of local alignment. All branch points in the computed RNA structure are found and used to divide the structure into smaller unbranched segments. Each segment is then realigned and backtracked in a normal fashion. Finally, the FOLDALIGN algorithm has also been updated with a better memory implementation and an improved energy model. With these improvements in the algorithm, the FOLDALIGN software package provides the molecular biologist with an efficient and user-friendly tool for searching for new ncRNAs. The software package is available for download at http://foldalign.ku.dk

DIAL: a web server for the pairwise alignment of two RNA three-dimensional structures using nucleotide, dihedral angle and base-pairing similarities

DIAL (dihedral alignment) is a web server that provides public access to a new dynamic programming algorithm for pairwise 3D structural alignment of RNA. DIAL achieves quadratic time by performing an alignment that accounts for (i) pseudo-dihedral and/or dihedral angle similarity, (ii) nucleotide sequence similarity and (iii) nucleotide base-pairing similarity

The PETfold and PETcofold web servers for intra- and intermolecular structures of multiple RNA sequences

The function of non-coding RNA genes largely depends on their secondary structure and the interaction with other molecules. Thus, an accurate prediction of secondary structure and RNA–RNA interaction is essential for the understanding of biological roles and pathways associated with a specific RNA gene. We present web servers to analyze multiple RNA sequences for common RNA structure and for RNA interaction sites. The web servers are based on the recent PET (Probabilistic Evolutionary and Thermodynamic) models PETfold and PETcofold, but add user friendly features ranging from a graphical layer to interactive usage of the predictors. Additionally, the web servers provide direct access to annotated RNA alignments, such as the Rfam 10.0 database and multiple alignments of 16 vertebrate genomes with human. The web servers are freely available at: http://rth.dk/resources/petfold

A comprehensive comparison of comparative RNA structure prediction approaches

BACKGROUND: An increasing number of researchers have released novel RNA structure analysis and prediction algorithms for comparative approaches to structure prediction. Yet, independent benchmarking of these algorithms is rarely performed as is now common practice for protein-folding, gene-finding and multiple-sequence-alignment algorithms. RESULTS: Here we evaluate a number of RNA folding algorithms using reliable RNA data-sets and compare their relative performance. CONCLUSIONS: We conclude that comparative data can enhance structure prediction but structure-prediction-algorithms vary widely in terms of both sensitivity and selectivity across different lengths and homologies. Furthermore, we outline some directions for future research

Computational identification of new structured cis-regulatory elements in the 3'-untranslated region of human protein coding genes

Messenger ribonucleic acids (RNAs) contain a large number of cis-regulatory RNA elements that function in many types of post-transcriptional regulation. These cis-regulatory elements are often characterized by conserved structures and/or sequences. Although some classes are well known, given the wide range of RNA-interacting proteins in eukaryotes, it is likely that many new classes of cis-regulatory elements are yet to be discovered. An approach to this is to use computational methods that have the advantage of analysing genomic data, particularly comparative data on a large scale. In this study, a set of structural discovery algorithms was applied followed by support vector machine (SVM) classification. We trained a new classification model (CisRNA-SVM) on a set of known structured cis-regulatory elements from 3′-untranslated regions (UTRs) and successfully distinguished these and groups of cis-regulatory elements not been strained on from control genomic and shuffled sequences. The new method outperformed previous methods in classification of cis-regulatory RNA elements. This model was then used to predict new elements from cross-species conserved regions of human 3′-UTRs. Clustering of these elements identified new classes of potential cis-regulatory elements. The model, training and testing sets and novel human predictions are available at: http://mRNA.otago.ac.nz/CisRNA-SVM

Web-Beagle: a web server for the alignment of RNA secondary structures

Web-Beagle (http://beagle.bio.uniroma2.it) is a web server for the pairwise global or local alignment of RNA secondary structures. The server exploits a new encoding for RNA secondary structure and a substitution matrix of RNA structural elements to perform RNA structural alignments. The web server allows the user to compute up to 10 000 alignments in a single run, taking as input sets of RNA sequences and structures or primary sequences alone. In the latter case, the server computes the secondary structure prediction for the RNAs on-the-fly using RNAfold (free energy minimization). The user can also compare a set of input RNAs to one of five pre-compiled RNA datasets including lncRNAs and 3' UTRs. All types of comparison produce in output the pairwise alignments along with structural similarity and statistical significance measures for each resulting alignment. A graphical color-coded representation of the alignments allows the user to easily identify structural similarities between RNAs. Web-Beagle can be used for finding structurally related regions in two or more RNAs, for the identification of homologous regions or for functional annotation. Benchmark tests show that Web-Beagle has lower computational complexity, running time and better performances than other available methods

DotAligner:Identification and clustering of RNA structure motifs

Abstract The diversity of processed transcripts in eukaryotic genomes poses a challenge for the classification of their biological functions. Sparse sequence conservation in non-coding sequences and the unreliable nature of RNA structure predictions further exacerbate this conundrum. Here, we describe a computational method, DotAligner, for the unsupervised discovery and classification of homologous RNA structure motifs from a set of sequences of interest. Our approach outperforms comparable algorithms at clustering known RNA structure families, both in speed and accuracy. It identifies clusters of known and novel structure motifs from ENCODE immunoprecipitation data for 44 RNA-binding proteins

e-RNA: a collection of web servers for comparative RNA structure prediction and visualisation

e-RNA offers a free and open-access collection of five published RNA sequence analysis tools, each solving specific problems not readily addressed by other available tools. Given multiple sequence alignments, Transat detects all conserved helices, including those expected in a final structure, but also transient, alternative and pseudo-knotted helices. RNA-Decoder uses unique evolutionary models to detect conserved RNA secondary structure in alignments which may be partly protein-coding. SimulFold simultaneously co-estimates the potentially pseudo-knotted conserved structure, alignment and phylogenetic tree for a set of homologous input sequences. CoFold predicts the minimum-free energy structure for an input sequence while taking the effects of co-transcriptional folding into account, thereby greatly improving the prediction accuracy for long sequences. R-chie is a program to visualise RNA secondary structures as arc diagrams, allowing for easy comparison and analysis of conserved base-pairs and quantitative features. The web site server dispatches user jobs to a cluster, where up to 100 jobs can be processed in parallel. Upon job completion, users can retrieve their results via a bookmarked or emailed link. e-RNA is located at http://www.e-rna.org