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Cellular Pathway Mapping Using Gene Expression Profiles and Upstream Elements

Cellular Pathway Mapping Using Gene Expression Profiles and Upstream Elements. Presentation By: Melanie Smith. Overview. Goal: Identify Gene Function Tool: Random Forest Classification Model Summer 1: Gene Expression Profiles

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Cellular Pathway Mapping Using Gene Expression Profiles and Upstream Elements

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  1. Cellular Pathway Mapping Using Gene Expression Profiles and Upstream Elements Presentation By: Melanie Smith

  2. Overview • Goal: Identify Gene Function • Tool: Random Forest Classification Model • Summer 1: Gene Expression Profiles • Summer 2: Upstream Transcription Factor Binding Sites (Regulation Elements)

  3. 21 Pathways From Kyoto Encyclopedia of Genes and Genomes • Genetic Information Processing • Ribosome • Polymerases • tRNA • Proteasome • Cellular Processes • Cell Cycle • Apoptosis • Cell Adhesion • Environmental Information Processing • MAP Kinase • PI Kinase • Human Diseases • Huntington’s Disease • Metabolism • Arginine and Proline • N-glycans • Glycolysis • Oxidative Phosphorylation • TCA Cycle • Pyrimidine • Glutathione • Valine, Leucine, Isoleucine • Porphyrin • Purine • Glycerolipids

  4. Goal Outcomes • Gene Identity • Shows what genes are affected by drugs in silico • Gene Network • Shows what genes are in a target pathway • Can explain drug side effects • Regulation Elements • Target regulators of pathways for drug therapy

  5. Tool: Random Forest

  6. Summer I • Question: How Do Pathways Relate? • Approach: • Microarrays from 60 Cell Lines • Gene Expression Profiles • Random Forest and Neural Network Classification Models • ID Gene • Find Related Pathways • Build a Network

  7. Summer II • Question: How do Pathways Relate? • Approach 2 • 7,700 genes, 21 Pathways, 301 Elements • Random Forest Classification Model • ID Gene • ID Important Regulation Elements for Each Pathway

  8. Is The Model Working? • 6 Pathways Identified 50 to 90% Error • Bugs? • Genes in a pathway may not share elements • Pathways Artificially Defined • Cell Functions may overlap in regulation

  9. Some Results • Pathway: Protein Synthesis (Ribosome Genes) • Proteins that Bind to Elements • ELK 1 and 4 – promote cell proliferation and differentiation • In Ras-raf-MAPK Signaling Cascade • MZF- Myeloid Zinc Finger • Regulates c-myb • C-myb participant of • Immature liver cell proliferation • T Cell development in Thymus • TBP- TATA Binding Protein

  10. Ending The Summer

  11. Future Paths • Combine Models • Gene Expression Profiles and Upstream Elements • Add More • Methylation, Acetylation, Phosphorylation… • Outcome • A fairly accurate Gene Prediction Model

  12. Questions?

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