An image processing approach to computing distances between RNA secondary structures dot plots

<p>Abstract</p> <p>Background</p> <p>Computing the distance between two RNA secondary structures can contribute in understanding the functional relationship between them. When used repeatedly, such a procedure may lead to finding a query RNA structure of interest in a database of structures. Several methods are available for computing distances between RNAs represented as strings or graphs, but none utilize the RNA representation with dot plots. Since dot plots are essentially digital images, there is a clear motivation to devise an algorithm for computing the distance between dot plots based on image processing methods.</p> <p>Results</p> <p>We have developed a new metric dubbed 'DoPloCompare', which compares two RNA structures. The method is based on comparing dot plot diagrams that represent the secondary structures. When analyzing two diagrams and motivated by image processing, the distance is based on a combination of histogram correlations and a geometrical distance measure. We introduce, describe, and illustrate the procedure by two applications that utilize this metric on RNA sequences. The first application is the RNA design problem, where the goal is to find the nucleotide sequence for a given secondary structure. Examples where our proposed distance measure outperforms others are given. The second application locates peculiar point mutations that induce significant structural alternations relative to the wild type predicted secondary structure. The approach reported in the past to solve this problem was tested on several RNA sequences with known secondary structures to affirm their prediction, as well as on a data set of ribosomal pieces. These pieces were computationally cut from a ribosome for which an experimentally derived secondary structure is available, and on each piece the prediction conveys similarity to the experimental result. Our newly proposed distance measure shows benefit in this problem as well when compared to standard methods used for assessing the distance similarity between two RNA secondary structures.</p> <p>Conclusion</p> <p>Inspired by image processing and the dot plot representation for RNA secondary structure, we have managed to provide a conceptually new and potentially beneficial metric for comparing two RNA secondary structures. We illustrated our approach on the RNA design problem, as well as on an application that utilizes the distance measure to detect conformational rearranging point mutations in an RNA sequence.</p

RNAexinv: An extended inverse RNA folding from shape and physical attributes to sequences

Abstract Background RNAexinv is an interactive java application that performs RNA sequence design, constrained to yield a specific RNA shape and physical attributes. It is an extended inverse RNA folding program with the rationale behind that the generated sequences should not only fold into a desired structure, but they should also exhibit favorable attributes such as thermodynamic stability and mutational robustness. RNAexinv considers not only the secondary structure in order to design sequences, but also the mutational robustness and the minimum free energy. The sequences that are generated may not fully conform with the given RNA secondary structure, but they will strictly conform with the RNA shape of the given secondary structure and thereby take into consideration the recommended values of thermodynamic stability and mutational robustness that are provided. Results The output consists of designed sequences that are generated by the proposed method. Selecting a sequence displays the secondary structure drawings of the target and the predicted fold of the sequence, including some basic information about the desired and achieved thermodynamic stability and mutational robustness. RNAexinv can be used successfully without prior experience, simply specifying an initial RNA secondary structure in dot-bracket notation and numerical values for the desired neutrality and minimum free energy. The package runs under LINUX operating system. Secondary structure predictions are performed using the Vienna RNA package. Conclusions RNAexinv is a user friendly tool that can be used for RNA sequence design. It is especially useful in cases where a functional stem-loop structure of a natural sequence should be strictly kept in the designed sequences but a distant motif in the rest of the structure may contain one more or less nucleotide at the expense of another, as long as the global shape is preserved. This allows the insertion of physical observables as constraints. RNAexinv is available at http://www.cs.bgu.ac.il/~RNAexinv. </jats:sec

RNAfbinv: an interactive Java application for fragment-based design of RNA sequences

Abstract Summary: In RNA design problems, it is plausible to assume that the user would be interested in preserving a particular RNA secondary structure motif, or fragment, for biological reasons. The preservation could be in structure or sequence, or both. Thus, the inverse RNA folding problem could benefit from considering fragment constraints. We have developed a new interactive Java application called RNA fragment-based inverse that allows users to insert an RNA secondary structure in dot-bracket notation. It then performs sequence design that conforms to the shape of the input secondary structure, the specified thermodynamic stability, the specified mutational robustness and the user-selected fragment after shape decomposition. In this shape-based design approach, specific RNA structural motifs with known biological functions are strictly enforced, while others can possess more flexibility in their structure in favor of preserving physical attributes and additional constraints. Availability: RNAfbinv is freely available for download on the web at http://www.cs.bgu.ac.il/∼RNAexinv/RNAfbinv. The site contains a help file with an explanation regarding the exact use. Contact:  [email protected]</jats:p

Simulated heat-shock response for a control sequence in the vicinity of the <i>E.coli ibpA</i> RNA thermometer, but not containing the thermometer itself.

<p>No clustering of dots that may indicate a potential RNA thermometer is observed.</p