Title: Computational Methods for Locating and Analyzing Conserved Gene Regulatory DNA Elements
Abstract: This thesis presents methods for locating and analyzing cis–regulatory DNA elements involved with the regulation of gene expression in multicellular organisms. The regulation of gene expression is carried out by the combined effort of several transcription factor proteins collectively binding the DNA on the cis–regulatory elements. Only sparse knowledge of the ’genetic code’ of these elements exists today. An automatic tool for discovery of putative cis–regulatory elements could help their experimental analysis, which would result in a more detailed view of the cis–regulatory element structure and function. We have developed a computational model for the evolutionary conservation of cis–regulatory elements. The elements are modeled as evolutionarily conserved clusters of sequence–specific transcription factor binding sites. We give an efficient dynamic programming algorithm that locates the putative cis–regulatory elements and scores them according to the conservation model. A notable proportion of the high–scoring DNA sequences show transcriptional enhancer activity in transgenic mouse embryos. The conservation model includes four parameters whose optimal values are estimated with simulated annealing. With good parameter values the model discriminates well between the DNA sequences with evolutionarily conserved
Publication Year: 2007
Publication Date: 2007-11-23
Language: en
Type: article
Access and Citation
Cited By Count: 8
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