Trait heterogeneity, which exists when a trait has been defined with insufficient specificity such that it is actually two or more distinct traits, has been implicated as a confounding factor in traditional statistical genetics of complex human disease. In the absence of detailed phenotypic data collected consistently in combination with genetic data, unsupervised computational methodologies offer the potential for discovering underlying trait heterogeneity. The performance of three such methodsBayesian Classification, Hypergraph-Based Clustering, and Fuzzy k-Modes Clusteringthat are appropriate for categorical data were compared. Also tested was the ability of these methods to additionally detect trait heterogeneity in the presence of locus heterogeneity and gene-gene interaction, which are two other complicating factors in discovering genetic models of complex human disease. Bayesian Classification performed well under the simplest of genetic models simulated, and it outperformed the other two methods, with the exception that the Fuzzy k-Modes Clustering performed best on the most complex genetic model. Permutation testing showed that Bayesian Classification controlled Type I error very well but produced less desirable Type II error rates. Methodological limitations and future directions are discussed.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07182005-122343 |
| Date | 23 July 2005 |
| Creators | Thornton-Wells, Tricia Ann |
| Contributors | Thomas J. Palmeri, Jason H. Moore, Constantin F. Aliferis, Mike McDonald, Jonathan L. Haines |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07182005-122343/ |
| 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, dissertation, 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 Vanderbilt 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. |
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