| 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.
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