A Linear Inside-Outside Algorithm for Correcting Sequencing Errors in Structured RNAs
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.
KeywordsRNA mutations secondary structure
Unable to display preview. Download preview PDF.
- 3.Olsen, G., Woese, C.: Ribosomal RNA: a key to phylogeny. The FASEB Journal 7(1), 113–123 (1993)Google Scholar
- 8.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)Google Scholar
- 9.Waldispühl, J., Devadas, S., Berger, B., Clote, P.: Efficient Algorithms for Probing the RNA Mutation Landscape. PLoS Computational Biology 4(8), e1000124 (2008)Google Scholar
- 10.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)Google Scholar
- 13.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)Google Scholar
- 15.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/