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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.

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(A) A graphical explanation of the parameter c that controls the proportion of non-collinear blocks in a resulting alignment; (B) Number of inversions in the TF-map alignment of the human and mouse promoters (500 nucleotides) of the MMP13 gene (RefSeq: NM 002427 and NM 008607), using multiple values of c.
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Figure 5: (A) A graphical explanation of the parameter c that controls the proportion of non-collinear blocks in a resulting alignment; (B) Number of inversions in the TF-map alignment of the human and mouse promoters (500 nucleotides) of the MMP13 gene (RefSeq: NM 002427 and NM 008607), using multiple values of c.

Mentions: Let A and B be two TF-maps in which a previous match has been identified (represented as two circles in Figure 5(A)). Then, a second match between one element in A and another one in B is being processed (represented as two squares in Figure 5(A)). The dotted lines indicate that such a site in B can be located either on the left or on the right of the circle site in the same map. In the first case, a non-collinear alignment is produced; in the second case, a normal collinear alignment is constructed. The case in which the non-collinear match occurs in A can be similarly defined.


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

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

(A) A graphical explanation of the parameter c that controls the proportion of non-collinear blocks in a resulting alignment; (B) Number of inversions in the TF-map alignment of the human and mouse promoters (500 nucleotides) of the MMP13 gene (RefSeq: NM 002427 and NM 008607), using multiple values of c.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: (A) A graphical explanation of the parameter c that controls the proportion of non-collinear blocks in a resulting alignment; (B) Number of inversions in the TF-map alignment of the human and mouse promoters (500 nucleotides) of the MMP13 gene (RefSeq: NM 002427 and NM 008607), using multiple values of c.
Mentions: Let A and B be two TF-maps in which a previous match has been identified (represented as two circles in Figure 5(A)). Then, a second match between one element in A and another one in B is being processed (represented as two squares in Figure 5(A)). The dotted lines indicate that such a site in B can be located either on the left or on the right of the circle site in the same map. In the first case, a non-collinear alignment is produced; in the second case, a normal collinear alignment is constructed. The case in which the non-collinear match occurs in A can be similarly defined.

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