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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Boxplots showing the range of sensitivity and positive predictive value statistics for all pairwise alignments of the 5S rRNA sequences, at each gap penalty value tested

<p><b>Copyright information:</b></p><p>Taken from "Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?"</p><p>http://www.biomedcentral.com/1471-2105/8/190</p><p>BMC Bioinformatics 2007;8():190-190.</p><p>Published online 8 Jun 2007</p><p>PMCID:PMC1904245.</p><p></p

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)

<p><b>Copyright information:</b></p><p>Taken from "Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?"</p><p>http://www.biomedcentral.com/1471-2105/8/190</p><p>BMC Bioinformatics 2007;8():190-190.</p><p>Published online 8 Jun 2007</p><p>PMCID:PMC1904245.</p><p></p> Images produced by drawgram, from the Phylip package of programs [30]

Boxplots showing the range of sensitivity and positive predictive value statistics for all pairwise alignments of the tRNA sequences, at each gap penalty value tested

<p><b>Copyright information:</b></p><p>Taken from "Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?"</p><p>http://www.biomedcentral.com/1471-2105/8/190</p><p>BMC Bioinformatics 2007;8():190-190.</p><p>Published online 8 Jun 2007</p><p>PMCID:PMC1904245.</p><p></p