Abstract

BackgroundIdentifying approximately repeated patterns, or motifs, in DNA sequences from a set of co-regulated genes is an important step towards deciphering the complex gene regulatory networks and understanding gene functions.ResultsIn this work, we develop a novel motif finding algorithm (PSO+) using a population-based stochastic optimization technique called Particle Swarm Optimization (PSO), which has been shown to be effective in optimizing difficult multidimensional problems in continuous domains. We propose a modification of the standard PSO algorithm to handle discrete values, such as characters in DNA sequences. The algorithm provides several features. First, we use both consensus and position-specific weight matrix representations in our algorithm, taking advantage of the efficiency of the former and the accuracy of the latter. Furthermore, many real motifs contain gaps, but the existing methods usually ignore them or assume a user know their exact locations and lengths, which is usually impractical for real applications. In comparison, our method models gaps explicitly, and provides an easy solution to find gapped motifs without any detailed knowledge of gaps. Our method allows the presence of input sequences containing zero or multiple binding sites.ConclusionExperimental results on synthetic challenge problems as well as real biological sequences show that our method is both more efficient and more accurate than several existing algorithms, especially when gaps are present in the motifs.

Highlights

  • Identifying approximately repeated patterns, or motifs, in DNA sequences from a set of co-regulated genes is an important step towards deciphering the complex gene regulatory networks and understanding gene functions

  • The existing algorithms can be roughly classified into two broad categories according to the motif representations: those based on position-specific weight matrices (PWMs), and those based on consensus sequences

  • We proposed a motif finding algorithm based on the classical Particle Swarm Optimization (PSO) strategy [12], where we used the set of positions on each sequence together as a solution, and searched the solution space by PSO algorithm

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Summary

Introduction

Identifying approximately repeated patterns, or motifs, in DNA sequences from a set of co-regulated genes is an important step towards deciphering the complex gene regulatory networks and understanding gene functions. Computational prediction of transcription factor binding sites (TFBS) from co-expressed/ co-regulated genes is an important step towards deciphering complex gene regulatory networks and understanding gene functions. The existing algorithms can be roughly classified into two broad categories according to the motif representations: those based on position-specific weight matrices (PWMs), and those based on consensus sequences. Examples of the former include well-known programs such as MEME [2], AlignACE [3], GibbsSampler [4], and BioProspector [5]. For an excellent survey of the existing methods and an assessment of their relative performance, see [1,8]

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