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Transat : a method for detecting evolutionarily conserved helices in alignments of RNA sequences and its application in identifying transient or alternative RNA structures Wiebe, Nicholas J. P.


The secondary structure of RNA molecules is often critical to their proper functioning, and so prediction of those structures has been a focus of bioinformatics research for many years. RNA folds as it is transcribed, and it has lately become apparent that the sequences of structures that an RNA adopts (its folding path) is vitally important for the RNA to fold into its proper structure. Analysis of the evolution of a group of related RNAs is useful for identifying conserved and therefore functionally important secondary structures. In theory, functional but transient secondary structures which play a role in the folding pathway should also be detectable in this way. Moreover, folding may be affected by a variety of factors in the cellular environment, which presents a challenge to the existing methods of RNA pathway prediction via simulation. Evolutionarily conserved helices are implicitly the ones formed in vivo, and so is a useful means of accounting for this problem. Here we present TRANSAT, a method of identifying evolutionarily conserved elements of RNA secondary structure, including transient structures, from an alignment of related RNAs. We evaluate TRANSAT’s performance on a wide variety of alignments, present some examples of its predictions, and show how its predictions may be useful for predicting folding pathways. We also present a method of generating simulated alignments, and use these alignments to examine TRANSAT’s performance in ways that are challenging with alignments of real sequences.

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