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Structure-based multiple RNA sequence alignment and finding RNA motifs

by Sarver, Michael Wayne.

Abstract (Summary)
ii Craig Zirbel, Advisor With the advent of faster computers and the availability of RNA crystal structures we can now use more information to align homologous RNA sequences. We can take a crystal structure and construct a probabilistic model, based on a SCFG, of an RNA molecule. We construct objects called nodes that modularize the model into small pieces that are more manageable. Using this model we can take sequences that are similar to the sequence in the 3D crystal structure and look for the most probable way that the model could have generated the sequence. Then we can get a detailed description of how each node of the model could have generated the sequence. Using this information we can align sequences. Given a seed alignment we give a procedure to construct a 3D structural alignment quickly. In addition we show how the parameters from the model can be estimated. We also have the ability to do motif swaps using objects called alternative nodes. We have developed an algorithm to quickly search through RNA 3D structures to find motifs. This is accomplished by taking a query motif with m bases and finding the center of the heavy atoms for each base and then rotating it onto candidate motifs that have the same number of bases. Then we measure how good a fit the candidate is to the query by using a discrepancy that we define which involves the distance between bases and their relative orientations. A simple inequality allows us to quickly identify candidates whose discrepancy with the query motif will exceed a cutoff discrepancy. We use this to screen out the vast majority quickly. To my grandmother and grandfather. iii
Bibliographical Information:

Advisor:

School:Bowling Green State University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:nucleotide sequence

ISBN:

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