Comparison of dynamic programming and evolutionary algorithms for RNA secondary structure prediction

This paper builds on previous research from an EA used to predict secondary structure of RNA molecules. The EA predicts which specific canonical base pairs forms hydrogen bonds and helices. Three new thermodynamic models were integrated into our EA. The first based on a modification to our original base pair model. The last two, INN and INN-HB, add stacking-energies using base pair adjacencies. We have tested RNA sequences of lengths 122, 543, and 1494 nucleotides on a wide variety of operators and parameters settings. The accuracy of the predicted structures is compared to the known structures thus demonstrating the benefits of using stacking-energies in structure prediction. Some other improvements to our EA are also discussed.

The design of DNA sequences is critical for many research fields such as DNA self-assembly, DNA hybridization arrays, DNA computing, and PCR-based applications. DNA secondary structure prediction is the key part for these DNA nanotechnologies. In this paper, we present a dynamic programming algorithm to predict the secondary structure of single-stranded DNA tiles. The algorithm calculates all possible maximum matches based on the nearest-neighbour model and global energy minimization. Experimental results show that the algorithm performers significantly to predict secondary str uctures for single-stranded DNA tiles.

The function of an RNA molecule is primarily established by its physical shape. As current physical structure determination methods are time consuming and expensive, there is great interest in finding computational structure prediction methods. P-RnaPredict is a parallel evolutionary algorithm for RNA secondary structure prediction. Two sets of experiments are performed on 5 known structures from 3 RNA classes (5S rRNA, Group I intron 16S rRNA, and 16S rRNA). The first determines the actual speedup, and the second evaluates the performance of P-RnaPredict through comparison to mfold. P-RnaPredict succeeds in predicting structures with higher true positive base pair counts and lower false positives than mfold on specific sequences.

19] Computer modeling and display of RNA secondary and tertiary structures

Recent years, RNA secondary structure prediction has attracted much attention of many researchers, which is an important way to grasp the biochemical function of RNA. However, it is very difficult to predict the RNA secondary structure including pseudoknot, which has been identified to be an NP-complete problem. In this paper, a novel multimodal optimization evolutionary algorithm is proposed to optimize the decision space based on the minimum free energy to predict the secondary structure of RNA. Because there exist multiple equivalent secondary structures which represent the same minimum free energy, our algorithm maintain diversity in decision space to find multiple sets of secondary structure simultaneously. The performance of our algorithm is evaluated by PseudoBase instances and compared with some good prediction algorithms. The comparison results show that our method has higher accuracy in RNA secondary structure prediction.

Structure mapping experiments (using probes such as dimethyl sulfate [DMS], kethoxal, and T1 and V1 RNases) are used to determine the secondary structures of RNA molecules. The process is iterative, combining the results of several probes with constrained minimum free-energy calculations to produce a model of the structure. We aim to evaluate whether particular probes provide more structural information, and specifically, how noise in the data affects the predictions. Our approach involves generating "decoy" RNA structures (using the sFold Boltzmann sampling procedure) and evaluating whether we are able to identify the correct structure from this ensemble of structures. We show that with perfect information, we are always able to identify the optimal structure for five RNAs of known structure. We then collected orthogonal structure mapping data (DMS and RNase T1 digest) under several solution conditions using our high-throughput capillary automated footprinting analysis (CAFA) technique on two group I introns of known structure. Analysis of these data reveals the error rates in the data under optimal (low salt) and suboptimal solution conditions (high MgCl(2)). We show that despite these errors, our computational approach is less sensitive to experimental noise than traditional constraint-based structure prediction algorithms. Finally, we propose a novel approach for visualizing the interaction of chemical and enzymatic mapping data with RNA structure. We project the data onto the first two dimensions of a multidimensional scaling of the sFold-generated decoy structures. We are able to directly visualize the structural information content of structure mapping data and reconcile multiple data sets.

G-quadruplexes are abundant locally stable structural elements in nucleic acids. The combinatorial theory of RNA structures and the dynamic programming algorithms for RNA secondary structure prediction are extended here to incorporate G-quadruplexes using a simple but plausible energy model. With preliminary energy parameters, we find that the overwhelming majority of putative quadruplex-forming sequences in the human genome are likely to fold into canonical secondary structures instead. Stable G-quadruplexes are strongly enriched, however, in the 5'UTR of protein coding mRNAs.

A Bayesian statistical algorithm for RNA secondary structure prediction

Ribonucleic acid is vital in numerous stages of protein synthesis; it also possesses important functional and structural roles within the cell. The function of an RNA molecule within a particular organic system is principally determined by its structure. The current physical methods available for structure determination are time-consuming and expensive. Hence, computational methods for structure prediction are sought after. The energies involved by the formation of secondary structure elements are significantly greater than those of tertiary elements. Therefore, RNA structure prediction focuses on secondary structure. We present P-RnaPredict, a parallel evolutionary algorithm for RNA secondary structure prediction. The speedup provided by parallelization is investigated with five sequences, and a dramatic improvement in speedup is demonstrated, especially with longer sequences. An evaluation of the performance of P-RnaPredict in terms of prediction accuracy is made through comparison with 10 individual known structures from 3 RNA classes (5S rRNA, Group I intron 16S rRNA and 16S rRNA) and the mfold dynamic programming algorithm. P-RnaPredict is able to predict structures with higher true positive base pair counts and lower false positives than mfold on certain sequences. P-RnaPredict is available for non-commercial usage. Interested parties should contact Kay C. Wiese (wiese@cs.sfu.ca).

Ribonucleic Acid (RNA) has important structural and functional roles in the cell and plays roles in many stages of protein synthesis. The structure of RNA largely determines its function. Current physical methods for structure determination are time-consuming and expensive, thus the methods for the computational prediction of structure are necessary. Various algorithms that have been used for RNA structure prediction based in minimum free energy include dynamic programming (DP) and meta heuristic algorithms. One of the most recent meta heuristic algorithms is Musician's behavior-inspired harmony search (HS) algorithm that has been successful in numerous complex optimization problems. This paper builds on the previous work of the harmony search algorithm (HSRNAFold) which was used to find the RNA secondary structure with minimum free energy. In this paper, the accuracy of prediction is compared to the dynamic programming technique RNAFold. The results show that HSRNAFold is able to predict more accurate structures than RNAFold for all test sequences.

BackgroundThe secondary structure of RNA molecules is intimately related to their function and often more conserved than the sequence. Hence, the important task of searching databases for RNAs requires to match sequence-structure patterns. Unfortunately, current tools for this task have, in the best case, a running time that is only linear in the size of sequence databases. Furthermore, established index data structures for fast sequence matching, like suffix trees or arrays, cannot benefit from the complementarity constraints introduced by the secondary structure of RNAs.ResultsWe present a novel method and readily applicable software for time efficient matching of RNA sequence-structure patterns in sequence databases. Our approach is based on affix arrays, a recently introduced index data structure, preprocessed from the target database. Affix arrays support bidirectional pattern search, which is required for efficiently handling the structural constraints of the pattern. Structural patterns like stem-loops can be matched inside out, such that the loop region is matched first and then the pairing bases on the boundaries are matched consecutively. This allows to exploit base pairing information for search space reduction and leads to an expected running time that is sublinear in the size of the sequence database. The incorporation of a new chaining approach in the search of RNA sequence-structure patterns enables the description of molecules folding into complex secondary structures with multiple ordered patterns. The chaining approach removes spurious matches from the set of intermediate results, in particular of patterns with little specificity. In benchmark experiments on the Rfam database, our method runs up to two orders of magnitude faster than previous methods.ConclusionsThe presented method's sublinear expected running time makes it well suited for RNA sequence-structure pattern matching in large sequence databases. RNA molecules containing several stem-loop substructures can be described by multiple sequence-structure patterns and their matches are efficiently handled by a novel chaining method. Beyond our algorithmic contributions, we provide with Structator a complete and robust open-source software solution for index-based search of RNA sequence-structure patterns. The Structator software is available at http://www.zbh.uni-hamburg.de/Structator.

A microcomupter program for the computation of free energy of the secondary structure of RNA oligomers by Ninio's rules

Detecting conserved secondary structures in RNA molecules using constrained structural alignment

Fuzzy k-nearest neighbor method is a generalization of nearest neighbor method, the simplest algorithm for pattern classification. One of the important areas for application of the pattern classification is the protein secondary structure prediction, an important topic in the field of bioinformatics. In this work, we develop a parallel algorithm for protein secondary structure prediction, based on the fuzzy k-nearest neighbor method, that uses evolutionary profile obtained from PSI-BLAST (Position Specific Iterative Basic Local Sequence Alignment Tool) as the feature vectors.

One of the major challenges in bioinformatics is the prediction of protein secondary structures, which must take precision into account in order to make the understanding of protein function and interactions fluid. In this study, we analyze the hypeparameter behavior of the SVM (Support Vector Machine) algorithm for protein secondary structure prediction from non-homologous datasets. The aim is to optimize the fit of the various SVM hyperparameters such as kernel, regularization parameter C and gamma γ in order to improve accuracy and verify the impact of these combinations in the overall model. We used cross-validation and grid search techniques to facilitate the model's performance, and performed a thorough analysis of the results using metrics such as precision, accuracy, recall and F1-Score while developing suitable visualizations to see how the model performs. The results indicate that using the right combination of hyperparameters can potentially improve model performance. With regard to the choice of hyperparameters in SVM models in bioinformatics, this study highlights their importance particularly for non-homologous datasets in which highly variable sequences are often found.