Functional promoter modules can be defected by formal models independent of overall nucleoside sequence similarity

Motivation: Gene regulation often depends on functional modules which featu re 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 pr esent in other regulatory sequences. Results: We developed a new method (FastM) which combines a search algorith m for individual transcription factor binding sites (MatInspector) with a d istance correlation function. FastM allows fast definition of a model of co rrelated binding sires derived from as little as a single promoter or enhan cer ModelInspector results are suitable for evaluation of the significance of the model. We used FastM to define a model for the experimentally verifi ed NF kappa B/IRF1 regulatory module from the major histocompatibility comp lex (MHC) class I HLA-B gene promoter Analysis of a test set of sequences a s Ir ell as database searches with this model showed excellent correlation of the model with the biological function of the module. These results coul d 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 h ypothetical GRE-GRE module with viral sequences based on analysis of severa l GenBank sections with this module.