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

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun 2015, Ischia Island, Italy. LNCS, 201

Parameterized Strings: Algorithms and Applications

The parameterized string (p-string), a generalization of the traditional string, is composed of constant and parameter symbols. A parameterized match (p-match) exists between two p-strings if the constants match exactly and there exists a bijection between the parameter symbols. Historically, p-strings have been employed in source code cloning, plagiarism detection, and structural similarity between biological sequences. By handling the intricacies of the parameterized suffix, we can efficiently address complex applications with data structures also reusable in traditional matching scenarios. In this dissertation, we extend data structures for p-strings (and variants) to address sophisticated string computations.;We introduce a taxonomy of classes for longest factor problems. Using this taxonomy, we show an interesting connection between the parameterized longest previous factor (pLPF) and familiar data structures in string theory, including the border array, prefix array, longest common prefix array, and analogous p-string data structures. Exploiting this connection, we construct a multitude of data structures using the same general pLPF framework.;Before this dissertation, the p-match was defined predominately by the matching between uncompressed p-strings. Here, we introduce the compressed parameterized pattern match to find all p-matches between a pattern and a text, using only the pattern and a compressed form of the text. We present parameterized compression (p-compression) as a new way to losslessly compress data to support p-matching. Experimentally, it is shown that p-compression is competitive with standard compression schemes. Using p-compression, we address the compressed p-match independent of the underlying compression routine.;Currently, p-string theory lacks the capability to support indeterminate symbols, a staple essential for applications involving inexact matching such as in music analysis. In this work, we propose and efficiently address two new types of p-matching with indeterminate symbols. (1) We introduce the indeterminate parameterized match (ip-match) to permit matching with indeterminate holes in a p-string. We support the ip-match by introducing data structures that extend the prefix array. (2) From a different perspective, the equivalence parameterized match (e-match) evolves the p-match to consider intra-alphabet symbol classes as equivalence classes. We propose a method to perform the e-match using the p-string suffix array framework, i.e. the parameterized suffix array (pSA) and parameterized longest common prefix array (pLCP). Historically, direct constructions of the pSA and pLCP have suffered from quadratic time bounds in the worst-case. Here, we introduce new p-string theory to efficiently construct the pSA/pLCP and break the theoretical worst-case time barrier.;Biological applications have become a classical use of p-string theory. Here, we introduce the structural border array to provide a lightweight solution to the biologically-oriented variant of the p-match, i.e. the structural match (s-match) on structural strings (s-strings). Following the s-match, we show how to use s-string suffix structures to support various pattern matching problems involving RNA secondary structures. Finally, we propose/construct the forward stem matrix (FSM), a data structure to access RNA stem structures, and we apply the FSM to the detection of hairpins and pseudoknots in an RNA sequence.;This dissertation advances the state-of-the-art in p-string theory by developing data structures for p-strings/s-strings and using p-string/s-string theory in new and old contexts to address various applications. Due to the flexibility of the p-string/s-string, the data structures and algorithms in this work are also applicable to the myriad of problems in the string community that involve traditional strings

Structator: fast index-based search for RNA sequence-structure patterns

Background The secondary structure of RNA molecules is intimately related to their function and often more conserved than the sequence. Hence, the important task of searching databases for RNAs requires to match sequence-structure patterns. Unfortunately, current tools for this task have, in the best case, a running time that is only linear in the size of sequence databases. Furthermore, established index data structures for fast sequence matching, like suffix trees or arrays, cannot benefit from the complementarity constraints introduced by the secondary structure of RNAs. Results We present a novel method and readily applicable software for time efficient matching of RNA sequence-structure patterns in sequence databases. Our approach is based on affix arrays, a recently introduced index data structure, preprocessed from the target database. Affix arrays support bidirectional pattern search, which is required for efficiently handling the structural constraints of the pattern. Structural patterns like stem-loops can be matched inside out, such that the loop region is matched first and then the pairing bases on the boundaries are matched consecutively. This allows to exploit base pairing information for search space reduction and leads to an expected running time that is sublinear in the size of the sequence database. The incorporation of a new chaining approach in the search of RNA sequence-structure patterns enables the description of molecules folding into complex secondary structures with multiple ordered patterns. The chaining approach removes spurious matches from the set of intermediate results, in particular of patterns with little specificity. In benchmark experiments on the Rfam database, our method runs up to two orders of magnitude faster than previous methods. Conclusions The presented method's sublinear expected running time makes it well suited for RNA sequence-structure pattern matching in large sequence databases. RNA molecules containing several stem-loop substructures can be described by multiple sequence-structure patterns and their matches are efficiently handled by a novel chaining method. Beyond our algorithmic contributions, we provide with Structator a complete and robust open-source software solution for index-based search of RNA sequence-structure patterns. The Structator software is available at http://www.zbh.uni-hamburg.de/Structator webcite.Deutsche Forschungsgemeinschaft (grant WI 3628/1-1

Graph theoretic methods for the analysis of structural relationships in biological macromolecules

Subgraph isomorphism and maximum common subgraph isomorphism algorithms from graph theory provide an effective and an efficient way of identifying structural relationships between biological macromolecules. They thus provide a natural complement to the pattern matching algorithms that are used in bioinformatics to identify sequence relationships. Examples are provided of the use of graph theory to analyze proteins for which three-dimensional crystallographic or NMR structures are available, focusing on the use of the Bron-Kerbosch clique detection algorithm to identify common folding motifs and of the Ullmann subgraph isomorphism algorithm to identify patterns of amino acid residues. Our methods are also applicable to other types of biological macromolecule, such as carbohydrate and nucleic acid structures

A bijection between the set of nesting-similarity classes and L & P matchings

Matchings are frequently used to model RNA secondary structures; however, not all matchings can be realized as RNA motifs. One class of matchings, called the L $\&$ P matchings, is the most restrictive model for RNA secondary structures in the Largest Hairpin Family (LHF). The L $\&$ P matchings were enumerated in $2015$ by Jefferson, and they are equinumerous with the set of nesting-similarity classes of matchings, enumerated by Klazar. We provide a bijection between these two sets. This bijection preserves noncrossing matchings, and preserves the sequence obtained reading left to right of whether an edge begins or ends at that vertex.Comment: 9 pages, 7 figure

Multiple structural alignment for distantly related all b structures using TOPS pattern discovery and simulated annealing

Topsalign is a method that will structurally align diverse protein structures, for example, structural alignment of protein superfolds. All proteins within a superfold share the same fold but often have very low sequence identity and different biological and biochemical functions. There is often signi®cant structural diversity around the common scaffold of secondary structure elements of the fold. Topsalign uses topological descriptions of proteins. A pattern discovery algorithm identi®es equivalent secondary structure elements between a set of proteins and these are used to produce an initial multiple structure alignment. Simulated annealing is used to optimize the alignment. The output of Topsalign is a multiple structure-based sequence alignment and a 3D superposition of the structures. This method has been tested on three superfolds: the b jelly roll, TIM (a/b) barrel and the OB fold. Topsalign outperforms established methods on very diverse structures. Despite the pattern discovery working only on b strand secondary structure elements, Topsalign is shown to align TIM (a/b) barrel superfamilies, which contain both a helices and b strands