Title
An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs.
Abstract
Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty.We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed.The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven.
Year
DOI
Venue
2010
10.1186/1471-2105-11-551
BMC Bioinformatics
Keywords
Field
DocType
biological sciences,metabolism,transcription factors,binding sites,chemistry,transcription factor,high frequency,bioinformatics,microarrays,sequence motif,computational biology,transcription factor binding site,algorithms,dna sequence,dna
Transcription (biology),Binding site,DNA binding site,Biology,Fuzzy set,DNA,DNA sequencing,Bioinformatics,Genetics,Transcription factor,DNA microarray
Journal
Volume
Issue
ISSN
11
1
1471-2105
Citations 
PageRank 
References 
2
0.39
21
Authors
3
Name
Order
Citations
PageRank
Fernando Garcia-Alcalde120.73
A. Blanco214111.03
Adrian J. Shepherd327239.86