Title: "Globalizing the search for molecular regulators controlling the maturation of intestinal cells"
Speakers: Dr. James C. Fleet, Dept. of Foods and Nutrition and Dr. Jing Wu, Dept. of Statistics, Purdue University
Place: SMITH 108; Tuesday, 4:30pm


The number of genes identified as regulated in response to various conditions or stimuli in microarray-based screens is often far in excess of our a priori expectations. This presents a significant problem to biologists, i.e. which of the genes are directly regulated by the experimental stimuli? Binding of proteins (transcription factors) to specific DNA sequences (response elements) is necessary for the control of gene expression. Thus, identification of transcription factor binding sites within genes is a fundamental biological problem. Traditional methods to evaluate the regulation of individual genes are effective, but cumbersome and time consuming. Thus, gene-by-gene validation of microarray data is not feasible. In this seminar, we will discuss our plans to globalize the search for specific regulatory sequences in genes. Initially we propose to develop a bioinformatics tool based on the hidden semi-Markov model for identification of transcription factor binding sites in genomic sequences. Our search will focus on identification of genes containing binding sites for three transcription factors proposed to be involved in the differentiation of small intestinal cells: HNF-1, cdx-2, and GATA 4-6. The model we propose to search for the binding sites simultaneously, an approach that has a lower false positive rate than sequential use of traditional positional weight matrices. To reduce the high false positive rate associated with searches within the promoter of genes from a single species, we will apply our model only to sequences that are conserved between the human and mouse genomes. The positions of the binding sites in human and mouse sequences are given by the Viterbi algorithm.

See http://www.stat.purdue.edu/~doerge/BIOINFORM.D/SPRING04/sem.html for a full scheule of BIOINFORMATICS SEMINARS.