1. Cellular Profiles Exploring gene expression profile patterns Pathways, Profiles and Predictions Brad Windle Associate Professor of Medicinal Chemistry Ph. # 628-1956 email bwindle@hsc.vcu.edu

2. Profile A set of data that reflects something of significance Cellular Profile A set of data that reflects something of biological significance A cell profile- may relate to a property of the cell A cellular component profile- may relate to a property of the component Profiles are sometimes referred to as Signatures or Fingerprints

3. Cellular Profiles Gene Expression Protein Expression Misc Data SNPs Methylation Cell State Drug Response Metabolitics Structural Genomic Protein States Disease Gene/Protein Sequence Protein Structure Drug Structure

4. Cellular Profiles Gene Expression Protein Expression Misc Data SNPs Methylation Drug Response Metabolitics Structural Genomic Protein States Gene/Protein Sequence Protein Structure Drug Structure

5. cell or condition of interest control or reference cell hybridize to microarray Gene Expression Profiling

6. Comparative Genomic Hybridization (CGH) Structural Genomic Profiling cell with deletionsnormal cell hybridize to metaphase chromosomes

7. CGH-arrays cell with deletionsnormal cell hybridize to BAC arrays

8. Methylation Profiling me CG GC Isolate or enrich for methylated DNA total genomic DNA

9. Profiling Transcription Factor-Interactive DNA Immuno-precipitate w/ Ab to protein Chromatin IP or ChIP total genomic DNA

10. Combinatorial Elements Regulating Transcription

11. The ProfileData Sources SNPsDNA microarray, oligos, millions of SNP sites Protein expressionAb microarray, 2D gels, chromatographics Protein states2D gels, <1000 proteins resolved Drug responsebrute force, 70,000 compounds screened Metaboliticschromatographics DNA/protein sequenceSequencing, <20 people sequenced, brute force Drug structurein silico Protein structure3D crystallography, NMR, brute force Gene expressionDNA microarrays, oligo or PCR, 20-30,000 genes Structural genomicsDNA microarrays, BACs, ~one per 1Mb MethylationDNA microarrays, upstream sequences, CpG islands

12. Gene Expression Profile cell lines genes 1 2 3 4 1 2 3 4 5 6 7 8 9 histone modification protein synthesis

13. http://www.geneontology.org/ Classifying a Gene/Protein’s Function or Pathway

14. Exploring Gene Expression Profile Patterns We’ll start with exploring profiles for 6000 genes in the NCI 60 cell lines using the application Treeview.