Bioinformatics, Vol 15, 180-186, Copyright © 1999 by Oxford University Press
A Klingenhoff, K Frech, K Quandt and T Werner
MOTIVATION: Gene regulation often depends on functional modules which
feature a detectable internal organization. Overall sequence similarity of
these modules is often insufficient for detection by general search methods
like FASTA or even Gapped BLAST. However, it is of interest to evaluate
whether modules, often known from experimental analysis of single
sequences, are present in other regulatory sequences. RESULTS: We developed
a new method (FastM) which combines a search algorithm for individual
transcription factor binding sites (MatInspector) with a distance
correlation function. FastM allows fast definition of a model of correlated
binding sites derived from as little as a single promoter or enhancer.
ModelInspector results are suitable for evaluation of the significance of
the model. We used FastM to define a model for the experimentally verified
NFkappaB/IRF1 regulatory module from the major histocompatibility complex
(MHC) class I HLA-B gene promoter. Analysis of a test set of sequences as
well as database searches with this model showed excellent correlation of
the model with the biological function of the module. These results could
not be obtained by searches using FASTA or Gapped BLAST, which are based on
sequence similarity. We were also able to demonstrate association of a
hypothetical GRE-GRE module with viral sequences based on analysis of
several GenBank sections with this module. AVAILABILITY: The WWW version of
FastM is accessible at: http://www.gsf.de/cgi-bin/fastm. pl and
http://genomatix.gsf.de/cgi- bin/fastm2/fastm.pl
ARTICLES
Functional promoter modules can be detected by formal models independent of overall nucleotide sequence similarity
Institute of Mammalian Genetics, GSF-National Research Center for Environment and Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany.
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