Definitions

# List of RNA structure prediction software

This list of RNA structure prediction software is a compilation of software tools and web portals used for RNA structure prediction.

## Single sequence structure prediction

 Name Description Knots Links References CONTRAfold Secondary structure prediction method based on conditional log-linear models (CLLMs), a flexible class of probabilistic models which generalize upon SCFGs by using discriminative training and feature-rich scoring. no sourcecode webserver KineFold Folding kinetics of RNA sequences including pseudoknots. yes linuxbinary, webserver Mfold MFE RNA structure prediction algorithm. no sourcecode, webserver Pknots A dynamic programming algorithm for optimal RNA pseudoknot prediction using the nearest neighbour energy model. yes sourcecode PknotsRG A dynamic programming algorithm for the prediction of a restricted class of RNA pseudoknots. yes sourcecode, webserver RNAfold MFE RNA structure prediction algorithm. Includes an implementation of the partition function for computing basepair probabilities and circular RNA folding. no sourcecode, webserver Sfold Statistical sampling of all possible structures. The sampling is weighted by partition function probabilities. no webserver UNAFold The UNAFold software package is an integrated collection of programs that simulate folding, hybridization, and melting pathways for one or two single-stranded nucleic acid sequences. no sourcecode *Knots: Pseudoknot prediction, .

## Comparative methods

The single sequence methods mentioned above have a difficult job detecting a small sample of reasonable secondary structures from a large space of possible structures. A good way to reduce the size of the space is to use evolutionary approaches. Structures that have been conserved by evolution are far more likely to be the functional form. The methods below use this approach.

 Name Description Number of sequences Alignment Structure Knots Link References Carnac Comparative analysis combined with MFE folding. any no yes no sourcecode, webserver CMfinder an expectation maximization algorithm using covariance models for motif description. Uses heuristics for effective motif search, and a Bayesian framework for structure prediction combining folding energy and sequence covariation. $3le seqs le60$ yes yes no sourcecode, webserver CONSAN implements a pinned Sankoff algorithm for simultaneous pairwise RNA alignment and consensus structure prediction. 2 yes yes no sourcecode Dynalign an algorithm that improves the accuracy of structure prediction by combining free energy minimization and comparative sequence analysis to find a low free energy structure common to two sequences without requiring any sequence identity. 2 yes yes no sourcecode FoldalignM A multiple RNA structural RNA alignment method, to a large extend based on the PMcomp program. any yes yes no sourcecode KNetFold Computes a consensus RNA secondary structure from an RNA sequence alignment based on machine learning. any input yes yes linuxbinary, webserver LARA Produce a global fold and alignment of ncRNA families using integer linear programming and Lagrangian relaxation. any yes yes no sourcecode LocaRNA LocaRNA is the successor of PMcomp with an improved time complexity. It is a variant of Sankoff's algorithm for simultaneous folding and alignment, which takes as input pre-computed base pair probability matrices from McCaskill's algorithm as produced by RNAfold -p. Thus the method can also be viewed as way to compare base pair probability matrices. any yes yes no sourcecode MASTR A sampling approach using Markov chain Monte Carlo in a simulated annealing framework, where both structure and alignment is optimized by making small local changes. The score combines the log-likelihood of the alignment, a covariation term and the basepair probabilities. any yes yes no sourcecode Murlet a multiple alignment tool for RNA sequences using iterative alignment based on Sankoff's algorithm with sharply reduced computational time and memory. any yes yes no webserver MXSCARNA a multiple alignment tool for RNA sequences using progressive alignment based on pairwise structural alignment algorithm of SCARNA. any yes yes no webserver sourcecode PARTS A method for joint prediction of alignment and common secondary structures of two RNA sequences using a probabilistic model based on pseudo free energies obtained from precomputed base pairing and alignment probabilities. 2 yes yes no sourcecode Pfold Folds alignments using a SCFG trained on rRNA alignments. $le40$ input yes no webserver PMcomp/PMmulti PMcomp is a variant of Sankoff's algorithm for simultaneous folding and alignment, which takes as input pre-computed base pair probability matrices from McCaskill's algorithm as produced by RNAfold -p. Thus the method can also be viewed as way to compare base pair probability matrices. PMmulti is a wrapper program that does progressive multiple alignments by repeatedly calling pmcomp $2le seqs le6$ yes yes no sourcecode, webserver RNAalifold Folds precomputed alignments using a combination of free-energy and a covariation measures. Ships with the Vienna package. any input yes no link RNAcast enumerates the near-optimal abstract shape space, and predicts as the consensus an abstract shape common to all sequences, and for each sequence, the thermodynamically best structure which has this abstract shape. any no yes no sourcecode, webserver RNAforester Compare and align RNA secondary structures via a "forest alignment" approach. any yes input no sourcecode, webserver RNAmine Frequent stem pattern miner from unaligned RNA sequences is a software tool to extract the structural motifs from a set of RNA sequences. any no yes no webserver RNASampler A probabilistic sampling approach that combines intrasequence base pairing probabilities with intersequence base alignment probabilities. This is used to sample possible stems for each sequence and compare these stems between all pairs of sequences to predict a consensus structure for two sequences. The method is extended to predict the common structure conserved among multiple sequences by using a consistency-based score that incorporates information from all the pairwise structural alignments. any yes yes yes sourcecode SCARNA Stem Candidate Aligner for RNA (Scarna) is a fast, convenient tool for structural alignment of a pair of RNA sequences. It aligns two RNA sequences and calculates the similarities of them, based on the estimated common secondary structures. It works even for pseudoknotted secondary structures. 2 yes yes no webserver SimulFold simultaneously inferring RNA structures including pseudoknots, alignments, and trees using a Bayesian MCMC framework. any yes yes yes sourcecode Stemloc a program for pairwise RNA structural alignment based on probabilistic models of RNA structure known as Pair stochastic context-free grammars. any yes yes no sourcecode StrAl an alignment tool designed to provide multiple alignments of non-coding RNAs following a fast progressive strategy. It combines the thermodynamic base pairing information derived from RNAfold calculations in the form of base pairing probability vectors with the information of the primary sequence. $le50$ yes no no sourcecode, webserver WAR a webserver that makes it possible to simultaneously use a number of state of the art methods for performing multiple alignment and secondary structure prediction for noncoding RNA sequences. $2le seqs le50$ yes yes no webserver Xrate a program for analysis of multiple sequence alignments using phylogenetic grammars, that may be viewed as a flexible generalization of the "Pfold" program. any yes yes no sourcecode * Number of sequences: . * Alignment: predicts an alignment, . * Structure: predicts structure, . * Knots: pseudoknot prediction, .

## Inter molecular interactions: RNA-RNA

Many ncRNAs function by binding to other RNAs. For example, miRNAs regulate protein coding gene expression by binding to 3' UTRs, small nucleolar RNAs guide post-transcriptional modifications by binding to rRNA, U4 spliceosomal RNA and U6 spliceosomal RNA bind to each other forming part of the spliceosome and many small bacterial RNAs regulate gene expression by antisense interactions Eg. GcvB, OxyS and RyhB.

 Name Description miRNA specific Intra-molecular structure Comparative Link References RNAaliduplex Based upon RNAduplex with bonuses for covarying sites no no yes sourcecode RNAcofold works much like RNAfold, but allows to specify two RNA sequences which are then allowed to form a dimer structure. no yes no sourcecode RNAduplex computes optimal and suboptimal secondary structures for hybridization. The calculation is simplified by allowing only inter-molecular base pairs. no no no sourcecode RNAhybrid a tool for finding the minimum free energy hybridisation of a long and a short RNA. yes no no sourcecode, webserver RNAup calculates the thermodynamics of RNA-RNA interactions. RNA-RNA binding is decomposed into two stages. (1) First the probability that a sequence interval (e.g. a binding site) remains unpaired is computed. (2) Then the binding energy given that the binding site is unpaired is calculated as the optimum over all possible types of bindings. no yes no sourcecode * Number of sequences: . * Alignment: predicts an alignment, . * Structure: predicts structure, . * Knots: pseudoknot prediction, .

## ncRNA gene prediction software

 Name Description Number of sequences Alignment Structure Link References Alifoldz Assessing a multiple sequence alignment for the existence of an unusual stable and conserved RNA secondary structure. any input yes sourcecode EvoFold a comparative method for identifying functional RNA structures in multiple-sequence alignments. It is based on a probabilistic model-construction called a phylo-SCFG and exploits the characteristic differences of the substitution process in stem-pairing and unpaired regions to make its predictions. any input yes linuxbinary QRNA This is the code from Elena Rivas that accompanies a submitted manuscript "Noncoding RNA gene detection using camparative sequence analysis". QRNA uses comparative genome sequence analysis to detect conserved RNA secondary structures, including both ncRNA genes and cis-regulatory RNA structures. 2 input yes sourcecode RNAz program for predicting structurally conserved and thermodynamic stable RNA secondary structures in multiple sequence alignments. It can be used in genome wide screens to detect functional RNA structures, as found in noncoding RNAs and cis-acting regulatory elements of mRNAs. any input yes sourcecode, webserver Xrate a program for analysis of multiple sequence alignments using phylogenetic grammars, that may be viewed as a flexible generalization of the "Evofold" program. any yes yes sourcecode MSARi heuristic search for statistically significant conservation of RNA secondary structure in deep multiple sequence alignments. any input yes sourcecode * Number of sequences: . * Alignment: predicts an alignment, . * Structure: predicts structure, .

## Benchmarks

 Name Description Structure Alignment Phylogeny Links References BRalibase I A comprehensive comparison of comparative RNA structure prediction approaches yes no no data BRalibase II A benchmark of multiple sequence alignment programs upon structural RNAs no yes no data BRalibase III A critical assessment of the performance of homology search methods on noncoding RNA no yes no data * Alignment: benchmarks alignment tools . * Structure: benchmarks structure prediction tools .

## Viewers/Editors

 Name Description Alignment Structure Link References 4sale A tool for Synchronous RNA Sequence and Secondary Structure Alignment and Editing yes yes sourcecode Colorstock, SScolor, Raton Colorstock, a command-line script using ANSI terminal color; SScolor, a Perl script that generates static HTML pages; and Raton, an AJAX web application generating dynamic HTML. Each tool can be used to color RNA alignments by secondary structure and to visually highlight compensatory mutations in stems. yes yes sourcecode RALEE a major mode for the Emacs text editor. It provides functionality to aid the viewing and editing of multiple sequence alignments of structured RNAs. yes yes sourcecode SARSE A graphical sequence editor for working with structural alignments of RNA. yes yes sourcecode * Alignment: view and edit an alignment, . * Structure: view and edit structure,