Abstract
Analysis of the sequence-structure relationship in RNA molecules are essential to evolutionary studies but also to concrete applications such as error-correction methodologies in sequencing technologies. The prohibitive sizes of the mutational and conformational landscapes combined with the volume of data to proceed require efficient algorithms to compute sequence-structure properties. More specifically, here we aim to calculate which mutations increase the most the likelihood of a sequence to a given structure and RNA family.
In this paper, we introduce RNApyro, an efficient linear-time and space inside-outside algorithm that computes exact mutational probabilities under secondary structure and evolutionary constraints given as a multiple sequence alignment with a consensus structure. We develop a scoring scheme combining classical stacking base pair energies to novel isostericity scales, and apply our techniques to correct point-wise errors in 5s rRNA sequences. Our results suggest that RNApyro is a promising algorithm to complement existing tools in the NGS error-correction pipeline.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Zuckerkandl, E., Pauling, L.: Molecules as documents of evolutionary history. Journal of Theoretical Biology 8(2), 357–366 (1965)
Olsen, G.J., Lane, D.J., Giovannoni, S.J., Pace, N.R., Stahl, D.A.: Microbial ecology and evolution: a ribosomal RNA approach. Annual Review of Microbiology 40, 337–365 (1986)
Olsen, G., Woese, C.: Ribosomal RNA: a key to phylogeny. The FASEB Journal 7(1), 113–123 (1993)
Turnbaugh, P.J., Ley, R.E., Hamady, M., Fraser-Liggett, C.M., Knight, R., Gordon, J.I.: The Human Microbiome Project. Nature 449(7164), 804–810 (2007)
Quince, C., Lanzén, A., Curtis, T.P., Davenport, R.J., Hall, N., Head, I.M., Read, L.F., Sloan, W.T.: Accurate determination of microbial diversity from 454 pyrosequencing data. Nat. Methods 6(9), 639–641 (2009)
Kunin, V., Engelbrektson, A., Ochman, H., Hugenholtz, P.: Wrinkles in the rare biosphere: pyrosequencing errors can lead to artificial inflation of diversity estimates. Environmental Microbiology 12(1), 118–123 (2010)
Quinlan, A., Stewart, D., Strömberg, M., Marth, G.: Pyrobayes: an improved base caller for SNP discovery in pyrosequences. Nature Methods 5(2), 179–181 (2008)
Medvedev, P., Scott, E., Kakaradov, B., Pevzner, P.: Error correction of high-throughput sequencing datasets with non-uniform coverage. Bioinformatics 27(13), i137–i141 (2011)
Waldispühl, J., Devadas, S., Berger, B., Clote, P.: Efficient Algorithms for Probing the RNA Mutation Landscape. PLoS Computational Biology 4(8), e1000124 (2008)
Turner, D.H., Mathews, D.H.: NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Research 38(Database issue), D280–D282 (2010)
Stombaugh, J., Zirbel, C.L., Westhof, E., Leontis, N.B.: Frequency and isostericity of RNA base pairs. Nucleic Acids Research 37(7), 2294–2312 (2009)
Leontis, N.B., Westhof, E.: Geometric nomenclature and classification of RNA base pairs. RNA 7(4), 499–512 (2001)
Hori, H., Osawa, S.: Origin and Evolution of Organisms as Deduced from 5s Ribosomal RNA Sequences. Molecular Biology and Evolution 4(5), 445–472 (1987)
Lari, K., Young, S.: The estimation of stochastic context-free grammars using the Inside-Outside algorithm. Computer Speech & Language 4(1), 35–56 (1990)
Johansson, F., et al.: mpmath: a Python library for arbitrary-precision floating-point arithmetic (version 0.14) (February 2010), http://code.google.com/p/mpmath/
Li, W., Godzik, A.: Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22(13), 1658–1659 (2006)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Reinharz, V., Ponty, Y., Waldispühl, J. (2013). A Linear Inside-Outside Algorithm for Correcting Sequencing Errors in Structured RNAs. In: Deng, M., Jiang, R., Sun, F., Zhang, X. (eds) Research in Computational Molecular Biology. RECOMB 2013. Lecture Notes in Computer Science(), vol 7821. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37195-0_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-37195-0_17
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-37194-3
Online ISBN: 978-3-642-37195-0
eBook Packages: Computer ScienceComputer Science (R0)