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Description

CONREAL web server allows identification of transcription factor binding sites (TFBS) that are conserved between two [orthologous promoter] sequences. The predictions can be performed by four different methods (CONREAL-, LAGAN-, MAVID- and BLASTZ-based) and results can be compared to each other.

Input sequences

Provide a pair of orthologous sequences in FASTA format or, alternatively, type in ENSEMBL gene ID or keyword to retrieve sequences of interest from ENSEMBL database.

Search parameters

There are 3 parameters that can be set:
  1. PWM threshold - minimum relative score of a TFBS hit to be considered in the analysis, in percentages.
  2. Length of flanks - number of bases flanking a TFBS to include for calculating homology.
  3. Threshold for homology - minimal percentage of homology between two TFBS sites, including flanking sequences.
In addition, it is possible to specify sources of PWMs and alignment methods to use (CONREAL, LAGAN, MAVID or BLASTZ). Currently, CONREAL web server uses 81 vertebrate matrices form JASPAR database and 546 matrices from TRANSFAC database (v.8.4).

Interpretation of results

Output consists of a graph, alignment and a table with predicted TFBSs. A graph shows aligned positions in the orthologous sequences and the density of predicted TFBS, facilitating general assessment of predictions and identification of TFBS "hot spots". A pairwise alignment of sequences provides single nucleotide resolution information, whereas a table with predicted conserved TFBS, sorted by position in the alignment and linked to JASPAR and TRANSFAC databases, supplies more detailed information on the transcription factors. Furthermore, when multiple algorithms were selected for analysis, the overlap between predictions by the different algorithms is shown for every TFBS thus providing a means for evaluation of prediction reliability.

Citation

Berezikov E, Guryev V, Plasterk R.H., Cuppen E. (2004) CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting. Genome Res., 14, 170-178.

Berezikov E, Guryev V, Cuppen E. (2005) CONREAL Web Server: Identification and Visualization of Conserved Transcription Factor Binding Sites. In preparation.

Contact

Eigene Berezikov