Louse (Insecta : Phthiraptera) mitochondrial 12S rRNA secondary structure is highly variable

Lice are ectoparasitic insects hosted by birds and mammals. Mitochondrial 12S rRNA sequences obtained from lice show considerable length variation and are very difficult to align. We show that the louse 12S rRNA domain III secondary structure displays considerable variation compared to other insects, in both the shape and number of stems and loops. Phylogenetic trees constructed from tree edit distances between louse 12S rRNA structures do not closely resemble trees constructed from sequence data, suggesting that at least some of this structural variation has arisen independently in different louse lineages. Taken together with previous work on mitochondrial gene order and elevated rates of substitution in louse mitochondrial sequences, the structural variation in louse 12S rRNA confirms the highly distinctive nature of molecular evolution in these insects

Efficient alignment of RNA secondary structures using sparse dynamic programming

BACKGROUND: Current advances of the next-generation sequencing technology have revealed a large number of un-annotated RNA transcripts. Comparative study of the RNA structurome is an important approach to assess their biological functionalities. Due to the large sizes and abundance of the RNA transcripts, an efficient and accurate RNA structure-structure alignment algorithm is in urgent need to facilitate the comparative study. Despite the importance of the RNA secondary structure alignment problem, there are no computational tools available that provide high computational efficiency and accuracy. In this case, designing and implementing such an efficient and accurate RNA secondary structure alignment algorithm is highly desirable. RESULTS: In this work, through incorporating the sparse dynamic programming technique, we implemented an algorithm that has an O(n(3)) expected time complexity, where n is the average number of base pairs in the RNA structures. This complexity, which can be shown assuming the polymer-zeta property, is confirmed by our experiments. The resulting new RNA secondary structure alignment tool is called ERA. Benchmark results indicate that ERA can significantly speedup RNA structure-structure alignments compared to other state-of-the-art RNA alignment tools, while maintaining high alignment accuracy. CONCLUSIONS: Using the sparse dynamic programming technique, we are able to develop a new RNA secondary structure alignment tool that is both efficient and accurate. We anticipate that the new alignment algorithm ERA will significantly promote comparative RNA structure studies. The program, ERA, is freely available at http://genome.ucf.edu/ERA

Pattern discovery in trees : algorithms and applications to document and scientific data management

Ordered, labeled trees are trees in which each node has a label and the left-to-right order of its children (if it has any) is fixed. Such trees have many applications in vision, pattern recognition, molecular biology and natural language processing. In this dissertation we present algorithms for finding patterns in the ordered labeled trees. Specifically we study the largest approximately common substructure (LACS) problem for such trees. We consider a substructure of a tree T to be a connected subgraph of T. Given two trees T1, T2 and an integer d, the LACS problem is to find a substructure U1 of T1 and a substructure U2 of T2 such that U1 is within distance d of U2 and where there does not exist any other substructure V1 of T1 and V2 of T2 such that V1 and V2 satisfy the distance constraint and the sum of the sizes of V1 and V2 is greater than the sum of the sizes of U1 and U2. The LACS problem is motivated by the studies of document and RNA comparison. We consider two types of distance measures: the general edit distance and a restricted edit distance originated from Selkow. We present dynamic programming algorithms to solve the LACS problem based on the two distance measures. The algorithms run as fast as the best known algorithms for computing the distance of two trees when the distance allowed in the common substructures is a constant independent of the input trees. To demonstrate the utility of our algorithms, we discuss their applications to discovering motifs in multiple RNA secondary structures. Such an application shows an example of scientific data mining. We represent an RNA secondary structure by an ordered labeled tree based on a previously proposed scheme. The patterns in the trees are substructures that can differ in both substitutions and deletions/insertions of nodes of the trees. Our techniques incorporate approximate tree matching algorithms and novel heuristics for discovery and optimization. Experimental results obtained by running these algorithms on both generated data and RNA secondary structures show the good performance of the algorithms. It is shown that the optimization heuristics speed up the discovery algorithm by a factor of 10. Moreover, our optimized approach is 100,000 times faster than the brute force method. Finally we implement our techniques into a graphic toolbox that enables users to find repeated substructures in an RNA secondary structure as well as frequently occurring patterns in multiple RNA secondary structures pertaining to rhinovirus obtained from the National Cancer Institute. The system is implemented in C programming language and X windows and is fully operational on SUN workstations

A modular data analysis pipeline for the discovery of novel RNA motifs

This dissertation presents a modular software pipeline that searches collections of RNA sequences for novel RNA motifs. In this case the motifs incorporate elements of primary and secondary structure. The motif search pipeline breaks up sets of RNA sequences into shortened segments of RNA primary sequence. The shortened segments are then folded to obtain low energy secondary structures. The distance estimation module of the pipeline then calculates distances between the folded bricks, and then analyzes the resulting distance matrices for patterns;An initial implementation of the pipeline is applied to synthetic and biological data sets. This implementation introduces a new distance measure for comparing RNA sequences based on structural annotation of the folded sequence as well as a new data analysis technique called non-linear projection. The modular nature of the pipeline is then used to explore the relationships between several different distance measures on random data, synthetic data, and a biological data set consisting of iron response elements. It is shown that the different distance measures capture different relationships between the RNA sequences. The non-linear projection algorithm is used to produce 2-dimensional projections of the distance matrices which are examined via inspection and k-means multiclustering. The pipeline is able to successfully cluster synthetic RNA sequences based only on primary sequence data as well as the iron response elements data set. The dissertation also presents a preliminary analysis of a large biological data set of HIV sequences

Efficient algorithms for local forest similarity and forest pattern matching

Ordered labelled trees are trees where each node has a label and the left-to-right order among siblings is significant. Ordered labelled forests are sequences of ordered labelled trees. Ordered labelled trees and forests are useful structures for hierarchical data representation. Given two ordered labelled forests F and G, the local forest similarity is to compute two sub-forests F\u27 and G\u27 of F and G respectively such that they are the most similar over all the possible F\u27 and G\u27. Given a target forest F and a pattern forest G, the forest pattern matching problem is to compute a sub-forest F\u27 of F which is the most similar to G over all the possible F\u27. This thesis presents novel efficient algorithms for the local forest similarity problem and forest pattern matching problem for sub-forest. An application of the algorithms is that it can be used to locate the structural regions in RNA secondary structures which is the necessity data in RNA secondary structure prediction and function investigation. RNA is a chain molecular, mathematically it is a string over a four letter alphabet; in computational molecular biology, labeled ordered trees are used to represent RNA secondary structures

Strategies for measuring evolutionary conservation of RNA secondary structures

<p>Abstract</p> <p>Background</p> <p>Evolutionary conservation of RNA secondary structure is a typical feature of many functional non-coding RNAs. Since almost all of the available methods used for prediction and annotation of non-coding RNA genes rely on this evolutionary signature, accurate measures for structural conservation are essential.</p> <p>Results</p> <p>We systematically assessed the ability of various measures to detect conserved RNA structures in multiple sequence alignments. We tested three existing and eight novel strategies that are based on metrics of folding energies, metrics of single optimal structure predictions, and metrics of structure ensembles. We find that the folding energy based SCI score used in the RNAz program and a simple base-pair distance metric are by far the most accurate. The use of more complex metrics like for example tree editing does not improve performance. A variant of the SCI performed particularly well on highly conserved alignments and is thus a viable alternative when only little evolutionary information is available. Surprisingly, ensemble based methods that, in principle, could benefit from the additional information contained in sub-optimal structures, perform particularly poorly. As a general trend, we observed that methods that include a consensus structure prediction outperformed equivalent methods that only consider pairwise comparisons.</p> <p>Conclusion</p> <p>Structural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future RNA gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences.</p

A new procedure to analyze RNA non-branching structures

RNA structure prediction and structural motifs analysis are challenging tasks in the investigation of RNA function. We propose a novel procedure to detect structural motifs shared between two RNAs (a reference and a target). In particular, we developed two core modules: (i) nbRSSP_extractor, to assign a unique structure to the reference RNA encoded by a set of non-branching structures; (ii) SSD_finder, to detect structural motifs that the target RNA shares with the reference, by means of a new score function that rewards the relative distance of the target non-branching structures compared to the reference ones. We integrated these algorithms with already existing software to reach a coherent pipeline able to perform the following two main tasks: prediction of RNA structures (integration of RNALfold and nbRSSP_extractor) and search for chains of matches (integration of Structator and SSD_finder)

RNAspa: a shortest path approach for comparative prediction of the secondary structure of ncRNA molecules

<p>Abstract</p> <p>Background</p> <p>In recent years, RNA molecules that are not translated into proteins (ncRNAs) have drawn a great deal of attention, as they were shown to be involved in many cellular functions. One of the most important computational problems regarding ncRNA is to predict the secondary structure of a molecule from its sequence. In particular, we attempted to predict the secondary structure for a set of unaligned ncRNA molecules that are taken from the same family, and thus presumably have a similar structure.</p> <p>Results</p> <p>We developed the RNAspa program, which comparatively predicts the secondary structure for a set of ncRNA molecules in linear time in the number of molecules. We observed that in a list of several hundred suboptimal minimal free energy (MFE) predictions, as provided by the RNAsubopt program of the Vienna package, it is likely that at least one suggested structure would be similar to the true, correct one. The suboptimal solutions of each molecule are represented as a layer of vertices in a graph. The shortest path in this graph is the basis for structural predictions for the molecule. We also show that RNA secondary structures can be compared very rapidly by a simple string Edit-Distance algorithm with a minimal loss of accuracy. We show that this approach allows us to more deeply explore the suboptimal structure space.</p> <p>Conclusion</p> <p>The algorithm was tested on three datasets which include several ncRNA families taken from the Rfam database. These datasets allowed for comparison of the algorithm with other methods. In these tests, RNAspa performed better than four other programs.</p