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General Departmental Seminar Series

This is a Joint Seminar sponsored by the Department of Biostatistics and Medical Informatics and the Computation and Informatics in Biology and Medicine (CIBM) Training Program.

New Data Driven Research Paradigm for the Post Genome Era: A Transcription Regulation Example

Chip Lawrence, Scientific Director, Wadsworth Center

Friday, November 15, 2002, 1:00 pm

Pyle Center, 702 Langdon Street, Room 313


In the traditional hypothesis-driven biomedical research paradigm, the design of experiments to address specific prior hypotheses takes center stage. But with the genome era has come a large mass of fundamental biological data gathered without prior hypothesis, spawning a new "data- driven" paradigm. The coupling of this paradigm with high throughput experimental technologies promise to greatly accelerate biomedical research. Studies of transcription regulation in E.coli provide an example of the potential of this approach. Elucidating the transcription regulatory networks of species is a grand challenge of the post-genomic era. Toward that end we recently applied Bayesian algorithms with the goal of locating cis-regulatory sites via cross species comparison in proteobacteria (McCue et.al, NAR, 2001, Genome Research 2002). Application of these technologies to a study set of 166 E. coli genes revealed that 75% of our predictions overlap documented transcription regulatory sites by 10 bp. That the remaining predictions included bona fide TF binding sites was demonstrated by affinity purification of a putative transcription factor (YijC) bound to predicted but undocumented sites upstream of the fabA, fabB, and yqfA genes. Through application to the complete set of intergenic regions in E. coli, regulatory sites for 2097 genes were predicted and are available at http://www.wadsworth.org/resnres/bioinfo/. These sites represent a set of testable hypotheses. The challenge now is to scale up validation from three oligomers to thousands. The emergence of syntenic sequence from multiple vertebrate species offers similar opportunities for these species. I'll also report on identification of cis-regulatory elements based on recent extensions the human/mouse sequence comparison technology described by Wasserman et.al, (Nature Genetics, 2000).

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