1. ABSTRACT
   
2. MULTIPLE TF-MAP ALIGNMENTS
   
3. EXAMPLES
   
4. SOURCE CODE DISTRIBUTION
   
5. mmeta WEB SERVER
   
6. IF YOU ENCOUNTER PROBLEMS...
   
7. REFERENCES
   
8. AUTHORS AND ACKNOWLEDGEMENTS
   

ABSTRACT

 
The analysis of the promoter sequence of genes with similar expression patterns is a basic tool to annotate common regulatory elements. Multiple sequence alignments are on the basis of most comparative approaches. The characterization of regulatory regions from co-expressed genes at the sequence level, however, does not yield satisfactory results in many occasions as promoter regions of genes sharing similar expression programs often do not show nucleotide sequence conservation. In a recent approach to circumvent this limitation, we proposed to align the maps of predicted transcription factors (referred as TF-maps) instead of the nucleotide sequence of two related promoters, taking into account the label of the corresponding factor and the position in the primary sequence. We have now extended the basic algorithm to permit multiple promoter comparisons using the progressive alignment paradigm. In addition, non-collinear conservation blocks might now be identified in the resulting alignments. We have optimized the parameters of the algorithm in a small, but well-characterized collection of human-mouse-chicken-zebrafish orthologous gene promoters. Results in this dataset indicate that TF-map alignments are able to detect high-level regulatory conservation at the promoter and the 3'UTR gene regions, which cannot be detected by the typical sequence alignments. Two particular examples are introduced here to illustrate the power of the multiple TF-map alignments to characterize conserved regulatory elements in absence of sequence similarity. We consider this kind of approach can be extremely useful in the future to annotate potential transcription factor binding sites on sets of co-regulated genes from high-throughput expression experiments.

MULTIPLE TF-MAP ALIGNMENTS

 
You can find all of the information about the TF-map alignment in the following references:

• E. Blanco,R. Guigó and X. Messeguer
  "Multiple Non-Collinear Transcription Factor Map Alignment of Promoter Regions"
  BMC Bioinformatics 8:138 (2007).



• Supplementary Material: algorithms, mapping, datasets, training, results

EXAMPLES

 
The Actin, α-cardiac gene is analyzed here:

PROMOTER SEQUENCES: (FASTA, 500 bps)

• HUMAN: M13483
• MOUSE: M26773
• CHICKEN: NM_001031229
• ZEBRAFISH: NM_214784

TF-MAPS:

• JASPAR TOP-50 predictions (GFF, T=0.25):
  - 157 TFBSs (human)
  - 197 TFBSs (mouse)
  - 220 TFBSs (chicken)
  - 167 TFBSs (zebrafish)
  - 741 TFBSs (TOTAL)

TF-MAP ALIGNMENTS:

• Using JASPAR TOP-50:
  - Meta-alignment (α=0.5,λ=0.1,μ=1,&gamma=0)
  [2 seconds (*)]
  - Info about the process
  

EXPERIMENTAL ANNOTATIONS in ABS [entry A0028]

SOURCE CODE DISTRIBUTION

 
mmeta distribution contains several directories and files compressed in a tar.gz file. Source code and documentation files are included in the distribution, as well as several examples.

All of the files can be obtained from our ftp server:

mmeta v 1.0:

• mmeta v 1.0 full distribution: source code and documentation
  [DOWNLOAD]
  
  - Instructions to install mmeta in your computer.
  
  - Please, verify the check-sum file value:
  

  Type: md5sum mmeta_v1.0.May_07_2007.tar.gz
  -> 69d042d720647c589727ed9af47fa6fa mmeta_v1.0.May_07_2007.tar.gz
  




• mmeta v 1.0 Linux binary (gcc version 3.2.3 20030502, Red Hat Linux 3.2.3-24
  [DOWNLOAD]

WEB SERVER

 
A mmeta web server that implements several mapping functions as well as the multiple TF-map alignment is available to submit up to 10 sequences over the Internet.

Input sequence size is limited to 500 bps or 1000 TFBSs.

IF YOU ENCOUNTER PROBLEMS...

 
If you encounter problems using mmeta, or have suggestions on how to improve it, please send an e-mail to eblanco@imim.es

REFERENCES

• E. Blanco, R. Guigó and X. Messeguer
  "Multiple Non-collinear Transcription Factor Map Alignment of Promoter Regions"
  BMC Bioinformatics 8:138 (2007).
  
[PUBLICATION]


• E. Blanco, X. Messeguer, T.F. Smith and R. Guigó
  "Transcription Factor Map Alignment of Promoter Regions"
  PLOS Computational Biology 2(5): e49 (2006).
  [PUBLICATION]
  
  
• E. Blanco, D. Farre, M. Alba, X. Messeguer and R. Guigó
  "ABS: a database of Annotated regulatory Binding Sites from orthologous promoters."
  Nucleic Acids Research 34:D63-D67 (2006).
  [DATABASE][PUBLICATION]
  
  
• E. Blanco, X. Messeguer and R. Guigó
  "Novel computational methods to characterize regulatory regions."
  CSHL - Systems Biology (Poster), New York, USA (2004)
  
  
• E. Blanco, X. Messeguer and R. Guigó
  "Alignment of Promoter Regions by Mapping Nucleotide Sequences into
  Arrays of Transcription Factor Binding Motifs."
  VIIth RECOMB (Poster), Berlin, Germany (2003)
  
  
• M.S. Waterman, T. F. Smith and H. L. Katcher
  "Algorithms for restriction map comparisons",
  Nucleic Acids Research, 12:237-242 (1984).
  

AUTHORS AND ACKNOWLEDGEMENTS

 
The current version of mmeta has been written by Enrique Blanco, Roderic Guigó and Xavier Messeguer.