Promising Drug Targets Reverse Expression Signature Gene Expression Connectivity query Score Lamb et. al. “The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease,” Science, 2006. Looking For Drug Targets Using In-Silico Knockouts in a PPI Network Disease State Disease State + Drug Mutation signal from mutations inhibition Knockout of Good Drug Target Will Reverse the Disease-Related Effects Differentially expressed genes propagation g1 g2 g3 g4 g5 g6 g7 g8 g9 g10 Patient’s mutation data Knockout of Good Drug Target Will Reverse the Disease-Related Effects Differentially expressed genes propagation g1 g2 g3 g4 g5 ...

 

Need to Add to part 2 or 3 A. Chip-seq B. Deep sequencing for expression profiling C. Illumina? movie Genomics Summary A. Microarrays: expression profiling and other uses B. Global Gene Knockouts C. Global protein localization in yeast D. Global complex identification in yeast E. Global two-hybrid analysis in yeast and other organisms F. RNAi G. Transgenics, gene “knock-outs” (genetics not genomics) H. Human Genome Project, Next Generation Sequencing, and Comparative Genomics Yeast “Knockout” Library Delete YFG Delete all genes (individually) Disruption of “All” Yeast Genes • Approx 6000 genes • Make 6000 sets of disruption primers ...