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RNAdualPF: software to compute the dual partition function with sample applications in molecular evolution theory.

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dc.contributor.author Garcia-Martin, Juan Antonio
dc.contributor.author Bayegan, Amir H.
dc.contributor.author Dotu, Ivan
dc.contributor.author Clote, Peter
dc.date.accessioned 2016-11-21T09:24:24Z
dc.date.available 2016-11-21T09:24:24Z
dc.date.issued 2016
dc.identifier.citation Garcia-Martin JA, Bayegan AH, Dotu I, Clote P. RNAdualPF: software to compute the dual partition function with sample applications in molecular evolution theory. BMC Bioinformatics. 2016 Oct 19;17(1):424.
dc.identifier.issn 1471-2105
dc.identifier.uri http://hdl.handle.net/10230/27547
dc.description.abstract BACKGROUND: RNA inverse folding is the problem of finding one or more sequences that fold into a user-specified target structure s 0, i.e. whose minimum free energy secondary structure is identical to the target s 0. Here we consider the ensemble of all RNA sequences that have low free energy with respect to a given target s 0. RESULTS: We introduce the program RNAdualPF, which computes the dual partition function Z ∗, defined as the sum of Boltzmann factors exp(-E(a,s 0)/RT) of all RNA nucleotide sequences a compatible with target structure s 0. Using RNAdualPF, we efficiently sample RNA sequences that approximately fold into s 0, where additionally the user can specify IUPAC sequence constraints at certain positions, and whether to include dangles (energy terms for stacked, single-stranded nucleotides). Moreover, since we also compute the dual partition function Z ∗(k) over all sequences having GC-content k, the user can require that all sampled sequences have a precise, specified GC-content. Using Z ∗, we compute the dual expected energy 〈E ∗〉, and use it to show that natural RNAs from the Rfam 12.0 database have higher minimum free energy than expected, thus suggesting that functional RNAs are under evolutionary pressure to be only marginally thermodynamically stable. We show that C. elegans precursor microRNA (pre-miRNA) is significantly non-robust with respect to mutations, by comparing the robustness of each wild type pre-miRNA sequence with 2000 [resp. 500] sequences of the same GC-content generated by RNAdualPF, which approximately [resp. exactly] fold into the wild type target structure. We confirm and strengthen earlier findings that precursor microRNAs and bacterial small noncoding RNAs display plasticity, a measure of structural diversity. CONCLUSION: We describe RNAdualPF, which rapidly computes the dual partition function Z ∗ and samples sequences having low energy with respect to a target structure, allowing sequence constraints and specified GC-content. Using different inverse folding software, another group had earlier shown that pre-miRNA is mutationally robust, even controlling for compositional bias. Our opposite conclusion suggests a cautionary note that computationally based insights into molecular evolution may heavily depend on the software used. C/C++-software for RNAdualPF is available at http://bioinformatics.bc.edu/clotelab/RNAdualPF .
dc.description.sponsorship Funding for this research was provided by National Science Foundation grant DBI-1262439.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.rights © 2016 The Author(s).Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to theCreative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.uri https://creativecommons.org/publicdomain/zero/1.0/
dc.subject.other RNA
dc.title RNAdualPF: software to compute the dual partition function with sample applications in molecular evolution theory.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s12859-016-1280-6
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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