This thesis deals with the problem of detecting binding sites in coding regions. A new comparative analysis method is developed by improving an existing method called COSMO. / The inter-species sequence conservation observed in coding regions may be the result of two types of selective pressure: the selective pressure on the protein encoded and, sometimes, the selective pressure on the binding sites. To predict some region in coding regions as a binding site, one needs to make sure that the conservation observed in this region is not due to the selective pressure on the protein encoded. To achieve this, COSMO built a null model with only the selective pressure on the protein encoded and computed p-values for the observed conservation scores, conditional on the fixed set of amino acids observed at the leaves. / It is believed, however, that the selective pressure on the protein assumed in COSMO is overly strong. Consequently, some interesting regions may be left undetected. In this thesis, a new method, COSMO-2, is developed to relax this assumption. / The amino acids are first classified into a fixed number of overlapping functional classes by applying an expectation maximization algorithm on a protein database. Two probabilities for each gene position are then calculated: (i) the probability of observing a certain degree of conservation in the orthologous sequences generated under each class in the null model (i.e. the p-value of the observed conservation under each class); and (ii) the probability that the codon column associated with that gene position belongs to each class. The p-value of the observed conservation for each gene position is the sum of the products of the two probabilities for all classes. Regions with low p-values are identified as potential binding sites. / Five sets of orthologous genes are analyzed using COSMO-2. The results show that COSMO-2 can detect the interesting regions identified by COSMO and can detect more interesting regions than COSMO in some cases.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.97926 |
| Date | January 2006 |
| Creators | Chen, Hui, 1974- |
| Publisher | McGill University |
| 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 | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (School of Computer Science.) |
| Rights | © Hui Chen, 2006 |
| Relation | alephsysno: 002493473, proquestno: AAIMR24637, Theses scanned by UMI/ProQuest. |
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