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

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionsThe 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.

Fast online and index-based algorithms for approximate search of RNA sequence-structure patterns

“…As in [23], we also support the description of an RNA molecule by multiple ordered sequence-structure patterns. In this way, the molecule’s secondary structure is decomposed into a sequence of substructures described by independent sequence-structure patterns.…”

“…This makes their application to large databases challenging. Previously, we addressed this problem by presenting Structator [23], an ultra fast index-based bidirectional matching tool that achieves sublinear running time by exploiting base pair complementarity constraints for search space reduction.…”

“…In this way, the molecule’s secondary structure is decomposed into a sequence of substructures described by independent sequence-structure patterns. These patterns are efficiently aligned to the target sequences using one of our new algorithms and the results are combined with fast global and local chaining algorithms [23,26]. This allows a better balancing of running time, sensitivity, and specificity compared to searching with a single long pattern describing the complete sequence and secondary structure.…”

Rapid Annotation of Non-coding RNA Structures with a Parameterized Filtering Approach

“…Recent research in molecular biology has revealed that ncRNAs are of fundamental importance in many biological processes, such as gene regulation, chromosome replication and RNA modification [3,12,25]. Recently, since the amount of fully sequenced data has grown explosively, computational search tools have become an important alternative for searching homologous RNA structures in genomic sequences and recognizing new ncRNAs [6,7,11,13]. In general, a genome is scanned through by a computational search tool during the search procedure and each sequence segment in the genome is aligned to a structural model that describes the secondary structure of the searched family.…”

Logol: Expressive Pattern Matching in Sequences. Application to Ribosomal Frameshift Modeling

“…For instance, RNAmotif [13], RNAbob [6], Hypasearch [10,20] and Palingol [2] have been designed for the description of patterns as a succession of stems and loops, usually offering the possibility of choosing either a standard Watson-Crick pairing (A-U, G-C) or a pairing including Wobble (A-U, G-C, G-U). A more recent tool in this category, Structator [14], significantly improves the parsing time by making use of an index structure that is suited for the analysis of palindromic structures, the affix arrays. Patterns may also contain some sequence information on words that have to be present in particular places of the stems or the loops.…”