Asap: a framework for over-representation statistics for transcription factor binding sites.
BACKGROUND
In studies of gene regulation the efficient computational detection of over-represented transcription factor binding sites is an increasingly important aspect. Several published methods can be used for testing whether a set of hypothesised co-regulated genes share a common regulatory regime based on the occurrence of the modelled transcription factor binding sites. However there is little or no information available for guiding the end users choice of method. Furthermore it would be necessary to obtain several different software programs from various sources to make a well-founded choice.


METHODS
We introduce a software package, Asap, for fast searching with position weight matrices that include several standard methods for assessing over-representation. We have compared the ability of these methods to detect over-represented transcription factor binding sites in artificial promoter sequences. Controlling all aspects of our input data we are able to identify the optimal statistics across multiple threshold values and for sequence sets containing different distributions of transcription factor binding sites.


CONCLUSIONS
We show that our implementation is significantly faster than more naïve scanning algorithms when searching with many weight matrices in large sequence sets. When comparing the various statistics, we show that those based on binomial over-representation and Fisher's exact test performs almost equally good and better than the others. An online server is available at http://servers.binf.ku.dk/asap/.
Marstrand
Troels T
TT
Bioinformatics Centre, Department of Molecular Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Frellsen
Jes
J
Moltke
Ida
I
Thiim
Martin
M
Valen
Eivind
E
Retelska
Dorota
D
Krogh
Anders
A
D000465:Algorithms; D001665:Binding Sites; D015233:Models, Statistical; D012984:Software; D013997:Time Factors; D014157:Transcription Factors
D014157:Transcription Factors