Alternative splicing (AS) is an important post-transcriptional mechanism that increases protein diversity and may affect mRNA stability and translaftion efficiency. Despite its importance, our knowledge about its mechanism and regulation is very limited. Although it is known that the regulation of AS is influenced by multiple factors, most previous studies have focused on analyzing an individual regulator. In this dissertation, we apply three types of association rule mining techniques to discover cis-regulatory motifs or motif groups that are associated with specific AS patterns in mouse. General association rule mining for categorical attributes is used to find âmotif=>motifâ rules in gene groups that show similar exon skipping patterns. This method provides candidates for interacting motifs. Discretization-based and distribution-based quantitative association rule mining techniques are used to find âmotif => exon skipping profileâ rules. Many of the discovered motif candidates coincide with known splicing factor binding sites. Our ultimate goal is to find motifs and motif combinations that are involved in the dynamic regulation of AS. Based on our observations we hypothesize that some cis-regulatory elements affect AS only in combination with other elements. Interacting motifs show interesting differences to motifs that act individually. For example, interacting motif pairs are more conserved, they occur on average closer to the splice sites, motif pairs derived from distribution-based association rule mining, occur also in higher multiplicity. Based on these observations, we hypothesize that interacting cis-regulatory motifs might often correspond to weaker binding sites that occur in clusters close to the regulated splice sites.
|Date||11 August 2009|
|Contributors||Steffen Heber, Zhao-Bang Zeng, Barbara Sherry, Eric A. Stone|
|Source Sets||North Carolina State University|
|Rights||unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dis sertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.|
Page generated in 0.0025 seconds