Simultaneous alignment and structure prediction for three ribonucleic acid sequences

Title: Simultaneous alignment and structure prediction for three ribonucleic acid sequences
Authors: Masoumi, Beeta
Date: 2005
Abstract: The first step in modeling the structure of an RNA molecule is the prediction of its secondary structure. Many computational techniques have been developed for this task. One approach, comparative sequence analysis, stands out for its remarkably accurate predictions. However, the technique has proven to be notoriously difficult to automate. Consequently, comparative sequence analysis still involves considerable human intervention. Sankoff proposed a dynamic programming algorithm that can simultaneously solve the sequence alignment and folding problems for multiple sequences. It combines free energy minimization with comparative sequence analysis to improve the quality of secondary structure prediction. Dynalign has been the first implementation of this algorithm for two RNA sequences. Using more input sequences should improve the accuracy, reduce the likelihood that bad predictions are made, but also lower the sensitivity. To investigate these claims, we have extended the software system Dynalign to use three input sequences, rather than two, and tested our algorithm with 10 tRNAs and 13 5S rRNAs. Specifically, the following hypotheses were tested: (1) the use of three input sequences improves the average accuracy compared to predictions based on two input sequences. Since it should be less likely that all three input sequences simultaneously fold into a bad free energy minimum compared to predictions based on two sequences, (2) the worst prediction for any sequence should be more accurate when three input sequences are used rather than two. Finally, the consensus structure of three sequences is probably less representative of the individual sequences. Therefore, (3) the average coverage should be less compared to Dynalign.
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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