? We will continue the development of computer methods for analyzing gene regulation. We will further enhance methods to identify regulatory sites from the promoter regions of co-regulated genes with special emphasis on taking advantage of orthologous promoter regions from additional species. Included in the improvements will be better ways to identify multiple transcription factors that act coordinately to regulate gene expression. ? ? We will develop computational methods to help determine which transcription factors within a genome interact with which regulatory sites. The methods will be developed initially using bacterial genomes where a large number of genome sequences, from a wide range of phylogenetic distances, already exist. We will test the ability of different types of information, including genomic location, phylogenetic correlation and recognition code predictions, to aid in the identification of the associations between factors and sites. ? ? We will continue the development and enhancement of methods to predict RNA motifs composed of both sequence and structure constraints. We will go beyond the capabilities of programs like FOLDALIGN to detect conserved structures that are complex, including pseudoknots. Two approaches will be tested, one general one that should work on any collection of common RNA motifs and the other designed specifically to take advantage of phylogenetically conserved motifs in orthologous regions of multiple species. ? ? Each of these projects will be enhanced through collaborations with other groups, primarily experimentalists, who are interested in the application of our methods to their biological problems. ? ?
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