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Mapping gene regulatory pathways by assembly of physical and genetic interactions

presented by

Trey Ideker
Associate Professor
University of California, San Diego (UCSD)

February 28, 2008

W. M. Keck Foundation Amphitheater, TSRI


Background:

     Trey Ideker is working to develop large-scale, computer-aided models of biological signaling and regulatory pathways. New types of models, experimental strategies, and statistical frameworks are needed for integrating the enormous amount of data on mRNA expression, protein expression, and protein interactions arising in the wake of the Human Genome Project. These tools will be crucial to the success of Systems Biology, i.e., understanding biological systems as more than merely the sum of their parts.


     Ideker received bachelor's and master's degrees from MIT in Electrical Engineering and Computer Science, where he was elected to the HKN Engineering Honor Society and awarded the Northern Telecom/BNR prize for his work in digital circuit design. Encouraged by developments in the Human Genome Project, Ideker rapidly became interested in applying methods from computer science and engineering to the understanding of biological systems. Towards this goal, he obtained a Ph.D. in Molecular Biotechnology at the University of Washington and at the Institute for Systems Biology under Dr. Leroy Hood. He then moved to the Whitehead Institute for Biomedical Research, in Cambridge, Massachusetts, as the David Baltimore Fellow and Pfizer Fellow of Computational Biology. Dr. Ideker is currently a member of the Dept. of Bioengineering at U. C. San Diego, where he is Associate Professor. He serves on the advisory board of Genstruct and the BioCyc Project, has been a Bioinformatics Lecturer for STR, Inc., and holds several patents in the fields of microarray analysis and systems biology.

Abstract:

     Physical and genetic mapping data have become as important to Network Biology as they were to the Human Genome Project. Physical interaction maps are being constructed through systematic measurements of protein-protein, protein-DNA, and protein-small molecule interactions. Genetic interaction maps are being generated by large-scale screening of synthetic-lethals and epistasis, by multipoint gene association studies, and by mapping the effects of natural and prescribed genetic variations on gene expression.


     We are working on ways of integrating physical and genetic interaction maps to assemble models of gene regulatory pathways. These efforts face several challenges, including: increasing the coverage of each type of network; establishing methods to assemble individual interaction measurements into contiguous pathway models; and annotating these pathways with detailed functional information. Efforts in each of these areas will be described. Using integrative tools, we are constructing network models to explain the physiological response of yeast to DNA damaging agents.


Related Publications


Kelley, R. and Ideker, T. Systematic interpretation of genetic interactions using protein networks. Nature Biotechnology 23(5):561-566 (2005).


Suthram, S., Sittler, T., and Ideker, T. The Plasmodium network diverges from those of other species. Nature 437: (November 3, 2005).


Workman, CT., Mak, HC., McCuine, S., Tagne, JB., Agarwal, M., Ozier, O., Begley, TJ., Samson, LD., Ideker, T. A Systems Approach to Mapping DNA Damage Response Pathways. Science. 312 (5776):1054-1059 (2006).


Tan K, Shlomi T, Feizi H, Ideker T, Sharan R. Transcriptional regulation of protein complexes within and across species. Proc Natl Acad Sci USA. Jan 16 (2007).


Chuang, HY, Lee, E, Liu, YT, Lee, D, and Ideker, T. Network-based classification of breast cancer metastasis. Mol Syst Biol. 3:140 (2007).


Suthram, S., Beyer, A, and Ideker, T. eQED: An efficient method for interpreting eQTL associations. Mol Syst Biol. In press.


http://www.cytoscape.org/
http://www.cellcircuits.org/

http://www.pathblast.org/


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