<p>Large-scale, in vitro vaccine screening is an expensive and slow process, while rational vaccine design is faster and cheaper. As opposed to the emperical ways to design vaccines in biology laboratories, rational vaccine design models the structure of vaccines with computational approaches. Building an effective predictive computer model requires extensive knowledge of the process or phenomenon being modelled. Given current knowledge about the steps involved in immune system responses, computer models are currently focused on one or two of the most important and best known steps; for example: presentation of antigens by major histo-compatibility complex (MHC) molecules. In
this step, the MHC molecule selectively binds to some peptides derived from antigens and then
presents them to the T-cell. One current focus in rational vaccine design is prediction of peptides that can be bound by MHC.<p>Theoretically, predicting which peptides bind to a particular MHC molecule involves discovering patterns in known MHC-binding peptides and then searching for peptides which conform to these patterns in some new antigenic protein sequences. According to some previous work, Hidden Markov models (HMMs), a machine learning technique, is one of the most effective approaches for this task. Unfortunately, for computer models like HMMs, the number of the parameters to be determined is larger than the number which can be estimated from available training data.<p>Thus, heuristic approaches have to be developed to determine the parameters. In this research, two heuristic approaches are proposed. The rst initializes the HMM transition and emission probability matrices by assigning biological meanings to the states. The second approach tailors the structure of a fully connected HMM (fcHMM) to increase specicity. The effectiveness of these two approaches is tested on two human leukocyte antigens(HLA) alleles, HLA-A*0201 and HLAB* 3501. The results indicate that these approaches can improve predictive accuracy. Further, the HMM implementation incorporating the above heuristics can outperform a popular prole HMM (pHMM) program, HMMER, in terms of predictive accuracy.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-02232005-121948 |
| Date | 24 February 2005 |
| Creators | Zhang, Chenhong |
| Contributors | Zhang, W. J. (Chris), Kusalik, Anthony J. (Tony), Daley, Mark, Bickis, Mikelis G., Babiuk, Lorne A. |
| Publisher | University of Saskatchewan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-02232005-121948/ |
| 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 University of Saskatchewan 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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