Limits...
Multiple non-collinear TF-map alignments of promoter regions.

Blanco E, Guigó R, Messeguer X - BMC Bioinformatics (2007)

Bottom Line: 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 addition, non-collinear conservation blocks might now be identified in the resulting alignments.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Grup d'Algorísmica i Genètica, Departament de Llenguatges i Sistemes Informàtics, Universitat Politècnica de Catalunya, C/Jordi Girona, 1-3, Barcelona, Catalonia, Spain. eblanco@imim.es <eblanco@imim.es>

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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. Three 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.

Show MeSH

Related in: MedlinePlus

Different forms to fill a dynamic programming matrix in during the alignment. For a current match between two alignments (denoted as a red square), the available area to search the best previous match when the matrix is processed row by row is depicted in green. For the same element, the additional area to search the best previous match when the matrix is processed diagonal by diagonal is depicted in blue. With the diagonal filling, a previous match (denoted as a red circle) that forms a non-collinear alignment can be detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1878506&req=5

Figure 4: Different forms to fill a dynamic programming matrix in during the alignment. For a current match between two alignments (denoted as a red square), the available area to search the best previous match when the matrix is processed row by row is depicted in green. For the same element, the additional area to search the best previous match when the matrix is processed diagonal by diagonal is depicted in blue. With the diagonal filling, a previous match (denoted as a red circle) that forms a non-collinear alignment can be detected.

Mentions: The non-collinear matches shown in Figure 3 can not be detected in the basic pairwise TF-map alignment algorithm [9]. Let A and B be two TF-maps in which two matches could form a non collinear alignment (represented as a circle and a square in Figure 4). The normal implementation fills the matrix in row by row, from top to bottom (or column by column, from left to right).


Multiple non-collinear TF-map alignments of promoter regions.

Blanco E, Guigó R, Messeguer X - BMC Bioinformatics (2007)

Different forms to fill a dynamic programming matrix in during the alignment. For a current match between two alignments (denoted as a red square), the available area to search the best previous match when the matrix is processed row by row is depicted in green. For the same element, the additional area to search the best previous match when the matrix is processed diagonal by diagonal is depicted in blue. With the diagonal filling, a previous match (denoted as a red circle) that forms a non-collinear alignment can be detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1878506&req=5

Figure 4: Different forms to fill a dynamic programming matrix in during the alignment. For a current match between two alignments (denoted as a red square), the available area to search the best previous match when the matrix is processed row by row is depicted in green. For the same element, the additional area to search the best previous match when the matrix is processed diagonal by diagonal is depicted in blue. With the diagonal filling, a previous match (denoted as a red circle) that forms a non-collinear alignment can be detected.
Mentions: The non-collinear matches shown in Figure 3 can not be detected in the basic pairwise TF-map alignment algorithm [9]. Let A and B be two TF-maps in which two matches could form a non collinear alignment (represented as a circle and a square in Figure 4). The normal implementation fills the matrix in row by row, from top to bottom (or column by column, from left to right).

Bottom Line: 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 addition, non-collinear conservation blocks might now be identified in the resulting alignments.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Grup d'Algorísmica i Genètica, Departament de Llenguatges i Sistemes Informàtics, Universitat Politècnica de Catalunya, C/Jordi Girona, 1-3, Barcelona, Catalonia, Spain. eblanco@imim.es <eblanco@imim.es>

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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. Three 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.

Show MeSH
Related in: MedlinePlus