Prospects and limitations of full-text index structures in genome analysis

The combination of incessant advances in sequencing technology producing large amounts of data and innovative bioinformatics approaches, designed to cope with this data flood, has led to new interesting results in the life sciences. Given the magnitude of sequence data to be processed, many bioinformatics tools rely on efficient solutions to a variety of complex string problems. These solutions include fast heuristic algorithms and advanced data structures, generally referred to as index structures. Although the importance of index structures is generally known to the bioinformatics community, the design and potency of these data structures, as well as their properties and limitations, are less understood. Moreover, the last decade has seen a boom in the number of variant index structures featuring complex and diverse memory-time trade-offs. This article brings a comprehensive state-of-the-art overview of the most popular index structures and their recently developed variants. Their features, interrelationships, the trade-offs they impose, but also their practical limitations, are explained and compared

An optimized TOPS+ comparison method for enhanced TOPS models

This article has been made available through the Brunel Open Access Publishing Fund.Background Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+. Results We have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method. Conclusions Our advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90 percent accuracy for SCOP alpha+beta; a 6 percent increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98 percent accuracy. Software Availability: The TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.This article is available through the Brunel Open Access Publishing Fun

A computer system to perform structure comparison using TOPS representations of protein structure

We describe the design and implementation of a fast topology–based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern matching algorithm for TOPS diagrams that we have designed and described elsewhere Gilbert et al. (1999). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web via the at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email

Secondary Indexing in One Dimension: Beyond B-trees and Bitmap Indexes

Let S be a finite, ordered alphabet, and let x = x_1 x_2 ... x_n be a string over S. A "secondary index" for x answers alphabet range queries of the form: Given a range [a_l,a_r] over S, return the set I_{[a_l;a_r]} = {i |x_i \in [a_l; a_r]}. Secondary indexes are heavily used in relational databases and scientific data analysis. It is well-known that the obvious solution, storing a dictionary for the position set associated with each character, does not always give optimal query time. In this paper we give the first theoretically optimal data structure for the secondary indexing problem. In the I/O model, the amount of data read when answering a query is within a constant factor of the minimum space needed to represent I_{[a_l;a_r]}, assuming that the size of internal memory is (|S| log n)^{delta} blocks, for some constant delta > 0. The space usage of the data structure is O(n log |S|) bits in the worst case, and we further show how to bound the size of the data structure in terms of the 0-th order entropy of x. We show how to support updates achieving various time-space trade-offs. We also consider an approximate version of the basic secondary indexing problem where a query reports a superset of I_{[a_l;a_r]} containing each element not in I_{[a_l;a_r]} with probability at most epsilon, where epsilon > 0 is the false positive probability. For this problem the amount of data that needs to be read by the query algorithm is reduced to O(|I_{[a_l;a_r]}| log(1/epsilon)) bits.Comment: 16 page