Abstract

BackgroundThe discovery of surprisingly frequent patterns is of paramount interest in bioinformatics and computational biology. Among the patterns considered, those consisting of pairs of solid words that co-occur within a prescribed maximum distance -or gapped factors- emerge in a variety of contexts of DNA and protein sequence analysis. A few algorithms and tools have been developed in connection with specific formulations of the problem, however, none can handle comprehensively each of the multiple ways in which the distance between the two terms in a pair may be defined.ResultsThis paper presents efficient algorithms and tools for the extraction of all pairs of words up to an arbitrarily large length that co-occur surprisingly often in close proximity within a sequence. Whereas the number of such pairs in a sequence of n characters can be Θ(n4), it is shown that an exhaustive discovery process can be carried out in O(n2) or O(n3), depending on the way distance is measured. This is made possible by a prudent combination of properties of pattern maximality and monotonicity of scores, which lead to reduce the number of word pairs to be weighed explicitly, while still producing also the scores attained by any of the pairs not explicitly considered. We applied our approach to the discovery of spaced dyads in DNA sequences.ConclusionsExperiments on biological datasets prove that the method is effective and much faster than exhaustive enumeration of candidate patterns. Software is available freely by academic users via the web interface at http://bcb.dei.unipd.it:8080/dyweb.

Highlights

  • The discovery of surprisingly frequent patterns is of paramount interest in bioinformatics and computational biology

  • A sequence of n characters may contain Θ(n2) distinct substrings, whence an exhaustive statistical index would be by one order larger than its subject

  • In previous work by [1], the size of such exhaustive tables has been shown to reduce to O(n) by a prudent combination of properties related to pattern maximality and monotonicity of scores

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Summary

Introduction

The discovery of surprisingly frequent patterns is of paramount interest in bioinformatics and computational biology. The computation of statistical indexes containing subword frequency counts, expectations, and scores thereof, arises routinely in the analysis of biological sequences. This problem is usually manageable when the word length is limited to some fixed, small value but rapidly escalates in complexity when applied on a genomic scale, perhaps without any length bound. We consider the problem of exhaustive counting and discovery of pairs of subwords that cooccur more frequently than expected within a specified distance in a sequence. In the literature, these patterns are refered to as gapped factors

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