The DOI matches its Crossref record; 91 of the 91 references it cites were found in a registry or an index.
A range of complex probabilistic models for RNA secondary structure prediction that includes the nearest-neighbor model and more
Open accessAbstract
The standard approach for single-sequence RNA secondary structure prediction uses a nearest-neighbor thermodynamic model with several thousand experimentally determined energy parameters. An attractive alternative is to use statistical approaches with parameters estimated from growing databases of structural RNAs. Good results have been reported for discriminative statistical methods using complex nearest-neighbor models, including CONTRAfold, Simfold, and ContextFold. Little work has been reported on generative probabilistic models (stochastic context-free grammars [SCFGs]) of comparable complexity, although probabilistic models are generally easier to train and to use. To explore a range of probabilistic models of increasing complexity, and to directly compare probabilistic, thermodynamic, and discriminative approaches, we created TORNADO, a computational tool that can parse a wide spectrum of RNA grammar architectures (including the standard nearest-neighbor model and more) using a generalized super-grammar that can be parameterized with probabilities, energies, or arbitrary scores. By using TORNADO, we find that probabilistic nearest-neighbor models perform comparably to (but not significantly better than) discriminative methods. We find that complex statistical models are prone to overfitting RNA structure and that evaluations should use structurally nonhomologous training and test data sets. Overfitting has affected at least one published method (ContextFold). The most important barrier to improving statistical approaches for RNA secondary structure prediction is the lack of diversity of well-curated single-sequence RNA secondary structures in current RNA databases.
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“Thus, the standard RNA secondary structure prediction problem can be cast as a parsing problem: given the above SCFG and an input RNA sequence, find the minimum-weight derivation in that can generate the sequence. This can be solved by the classical CKY algorithm from computational linguistics41–43.”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [43]
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Algorithm for optimized mRNA design improves stability and immunogenicity
Zhang, H., Zhang, L., Lin, A., Xu, C., Li, Z., Liu, K., Liu, B., Ma, X., Zhao, F., Jiang, H., et al. (2023) · Nature · doi:10.1038/s41586-023-06127-z · Cited by 531
RNA secondary structure prediction using deep learning with thermodynamic integration
Sato, K., Akiyama, M., & Sakakibara, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-21194-4 · Cited by 490
A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs
Rivas, E., Clements, J., & Eddy, S. R. (2016) · Nature Methods · doi:10.1038/nmeth.4066 · Cited by 381
Self-citationLinearFold: linear-time approximate RNA folding by 5'-to-3' dynamic programming and beam search
Huang, L., Zhang, H., Deng, D., Zhao, K., Liu, K., Hendrix, D. A., & Mathews, D. H. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz375 · Cited by 207
RNA secondary structure packages evaluated and improved by high-throughput experiments
Wayment-Steele, H. K., Kladwang, W., Strom, A. I., Lee, J., Treuille, A., Becka, A. J., Participants, E., & Das, R. (2022) · Nature Methods · doi:10.1038/s41592-022-01605-0 · Cited by 160
Metadata
- Authors
- Rivas, E., Lang, R., & Eddy, S. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Xavier University of Louisiana (US)
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-12-22
- Volume
- 18
- Issue
- 2
- Pages
- 193-212
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3264907
- OpenAlex
- W2109638684
- Cited by
- 145
- References
- 91
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 16 · 2023: 15 · 2022: 17 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 17 · 2012: 7
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- RNA (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM070538)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- RNA secondary structure prediction, probabilistic models, probabilistic context-free grammars, probabilistic generative models, overfitting, tornadoes, structural homology
- MeSH terms
- Algorithms, Models, Theoretical, Nucleic Acid Conformation, RNA, Software, Thermodynamics, Models, Statistical, Computational Biology, RNA Folding
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