Dataset Information

RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

ABSTRACT: BACKGROUND:Analysis of secondary structures is essential for understanding the functions of RNAs. Because RNA molecules thermally fluctuate, it is necessary to analyze the probability distributions of their secondary structures. Existing methods, however, are not applicable to long RNAs owing to their high computational complexity. Additionally, previous research has suffered from two numerical difficulties: overflow and significant numerical errors. RESULT:In this research, we reduced the computational complexity of calculating the landscape of the probability distribution of secondary structures by introducing a maximum-span constraint. In addition, we resolved numerical computation problems through two techniques: extended logsumexp and accuracy-guaranteed numerical computation. We analyzed the stability of the secondary structures of 16S ribosomal RNAs at various temperatures without overflow. The results obtained are consistent with previous research on thermophilic bacteria, suggesting that our method is applicable in thermal stability analysis. Furthermore, we quantitatively assessed numerical stability using our method.. CONCLUSION:These results demonstrate that the proposed method is applicable to long RNAs..

SUBMITTER: Takizawa H

PROVIDER: S-EPMC7245837 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

Takizawa Hiroki H Iwakiri Junichi J Asai Kiyoshi K

BMC bioinformatics 20200524 1

<h4>Background</h4>Analysis of secondary structures is essential for understanding the functions of RNAs. Because RNA molecules thermally fluctuate, it is necessary to analyze the probability distributions of their secondary structures. Existing methods, however, are not applicable to long RNAs owing to their high computational complexity. Additionally, previous research has suffered from two numerical difficulties: overflow and significant numerical errors.<h4>Result</h4>In this research, we re ...[more]

PMID: 32448174

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Project description:BackgroundImproving accuracy and efficiency of computational methods that predict pseudoknotted RNA secondary structures is an ongoing challenge. Existing methods based on free energy minimization tend to be very slow and are limited in the types of pseudoknots that they can predict. Incorporating known structural information can improve prediction accuracy; however, there are not many methods for prediction of pseudoknotted structures that can incorporate structural information as input. There is even less understanding of the relative robustness of these methods with respect to partial information.ResultsWe present a new method, Iterative HFold, for pseudoknotted RNA secondary structure prediction. Iterative HFold takes as input a pseudoknot-free structure, and produces a possibly pseudoknotted structure whose energy is at least as low as that of any (density-2) pseudoknotted structure containing the input structure. Iterative HFold leverages strengths of earlier methods, namely the fast running time of HFold, a method that is based on the hierarchical folding hypothesis, and the energy parameters of HotKnots V2.0.Our experimental evaluation on a large data set shows that Iterative HFold is robust with respect to partial information, with average accuracy on pseudoknotted structures steadily increasing from roughly 54% to 79% as the user provides up to 40% of the input structure.Iterative HFold is much faster than HotKnots V2.0, while having comparable accuracy. Iterative HFold also has significantly better accuracy than IPknot on our HK-PK and IP-pk168 data sets.ConclusionsIterative HFold is a robust method for prediction of pseudoknotted RNA secondary structures, whose accuracy with more than 5% information about true pseudoknot-free structures is better than that of IPknot, and with about 35% information about true pseudoknot-free structures compares well with that of HotKnots V2.0 while being significantly faster. Iterative HFold and all data used in this work are freely available at http://www.cs.ubc.ca/~hjabbari/software.php.

Project description:BackgroundOver the past years, statistical and Bayesian approaches have become increasingly appreciated to address the long-standing problem of computational RNA structure prediction. Recently, a novel probabilistic method for the prediction of RNA secondary structures from a single sequence has been studied which is based on generating statistically representative and reproducible samples of the entire ensemble of feasible structures for a particular input sequence. This method samples the possible foldings from a distribution implied by a sophisticated (traditional or length-dependent) stochastic context-free grammar (SCFG) that mirrors the standard thermodynamic model applied in modern physics-based prediction algorithms. Specifically, that grammar represents an exact probabilistic counterpart to the energy model underlying the Sfold software, which employs a sampling extension of the partition function (PF) approach to produce statistically representative subsets of the Boltzmann-weighted ensemble. Although both sampling approaches have the same worst-case time and space complexities, it has been indicated that they differ in performance (both with respect to prediction accuracy and quality of generated samples), where neither of these two competing approaches generally outperforms the other.ResultsIn this work, we will consider the SCFG based approach in order to perform an analysis on how the quality of generated sample sets and the corresponding prediction accuracy changes when different degrees of disturbances are incorporated into the needed sampling probabilities. This is motivated by the fact that if the results prove to be resistant to large errors on the distinct sampling probabilities (compared to the exact ones), then it will be an indication that these probabilities do not need to be computed exactly, but it may be sufficient and more efficient to approximate them. Thus, it might then be possible to decrease the worst-case time requirements of such an SCFG based sampling method without significant accuracy losses. If, on the other hand, the quality of sampled structures can be observed to strongly react to slight disturbances, there is little hope for improving the complexity by heuristic procedures. We hence provide a reliable test for the hypothesis that a heuristic method could be implemented to improve the time scaling of RNA secondary structure prediction in the worst-case - without sacrificing much of the accuracy of the results.ConclusionsOur experiments indicate that absolute errors generally lead to the generation of useless sample sets, whereas relative errors seem to have only small negative impact on both the predictive accuracy and the overall quality of resulting structure samples. Based on these observations, we present some useful ideas for developing a time-reduced sampling method guaranteeing an acceptable predictive accuracy. We also discuss some inherent drawbacks that arise in the context of approximation. The key results of this paper are crucial for the design of an efficient and competitive heuristic prediction method based on the increasingly accepted and attractive statistical sampling approach. This has indeed been indicated by the construction of prototype algorithms.

Dataset Information

RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

Publications

RintC: fast and accuracy-aware decomposition of distributions of RNA secondary structures with extended logsumexp.

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