Limits...
Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?

Bellamy-Royds AB, Turcotte M - BMC Bioinformatics (2007)

Bottom Line: In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm.However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Information Technology and Engineering, University of Ottawa, Ottawa, Ontario, Canada. turcotte@site.uottawa.ca <turcotte@site.uottawa.ca>

ABSTRACT

Background: In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.

Results: The research presented here investigates the possibility of applying a progressive, pairwise approach to the alignment of multiple RNA sequences by simultaneously predicting an energy-optimized consensus secondary structure. We take an existing algorithm for finding the secondary structure common to two RNA sequences, Dynalign, and alter it to align profiles of multiple sequences. We then explore the relative successes of different approaches to designing the tree that will guide progressive alignments of sequence profiles to create a multiple alignment and prediction of conserved structure.

Conclusion: We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm. However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.

Show MeSH

Related in: MedlinePlus

The phylogeny predicted by Clustal W for the 5S rRNA sequences (a), and the guide tree created by neighbour-joining the scores from the pairwise alignments with gap penalty of 4 kcal/mol (b). Images produced by drawgram, from the Phylip package of programs [30].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1904245&req=5

Figure 9: The phylogeny predicted by Clustal W for the 5S rRNA sequences (a), and the guide tree created by neighbour-joining the scores from the pairwise alignments with gap penalty of 4 kcal/mol (b). Images produced by drawgram, from the Phylip package of programs [30].

Mentions: For the 5S sequences, when the Clustal tree is compared against the neighbour-joining tree based on a gap penalty of 4 kcal/mol (Figure 9), the only topological differences are that the sequence V00336 is not added until the end, and the sequences X02627 and X04585 are joined together before being aligned with any other sequences. Nonetheless, these differences were sufficient to reduce the overall consensus structure from 11 predicted basepairs to six.


Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?

Bellamy-Royds AB, Turcotte M - BMC Bioinformatics (2007)

The phylogeny predicted by Clustal W for the 5S rRNA sequences (a), and the guide tree created by neighbour-joining the scores from the pairwise alignments with gap penalty of 4 kcal/mol (b). Images produced by drawgram, from the Phylip package of programs [30].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904245&req=5

Figure 9: The phylogeny predicted by Clustal W for the 5S rRNA sequences (a), and the guide tree created by neighbour-joining the scores from the pairwise alignments with gap penalty of 4 kcal/mol (b). Images produced by drawgram, from the Phylip package of programs [30].
Mentions: For the 5S sequences, when the Clustal tree is compared against the neighbour-joining tree based on a gap penalty of 4 kcal/mol (Figure 9), the only topological differences are that the sequence V00336 is not added until the end, and the sequences X02627 and X04585 are joined together before being aligned with any other sequences. Nonetheless, these differences were sufficient to reduce the overall consensus structure from 11 predicted basepairs to six.

Bottom Line: In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm.However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Information Technology and Engineering, University of Ottawa, Ottawa, Ontario, Canada. turcotte@site.uottawa.ca <turcotte@site.uottawa.ca>

ABSTRACT

Background: In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.

Results: The research presented here investigates the possibility of applying a progressive, pairwise approach to the alignment of multiple RNA sequences by simultaneously predicting an energy-optimized consensus secondary structure. We take an existing algorithm for finding the secondary structure common to two RNA sequences, Dynalign, and alter it to align profiles of multiple sequences. We then explore the relative successes of different approaches to designing the tree that will guide progressive alignments of sequence profiles to create a multiple alignment and prediction of conserved structure.

Conclusion: We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm. However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.

Show MeSH
Related in: MedlinePlus