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Cellular Pathway Mapping with Gene Expression Profiles & Regulatory Elements by Melanie Smith

This presentation by Melanie Smith focuses on using gene expression profiles and upstream elements to identify gene functions in cellular pathways. The goal is to develop a Random Forest Classification Model that can analyze 21 pathways from the Kyoto Encyclopedia of Genes and Genomes. The pathways cover genetic information processing, cellular processes, human diseases, and more. The outcomes include determining gene identity, understanding drug effects, and identifying pathway regulators for potential therapy. Two summer sessions delve into analyzing gene expression profiles and regulation elements to build a network of pathways. Results show insights into protein synthesis, signaling cascades, and cell proliferation. Future paths include combining models, incorporating additional elements like methylation and acetylation, and improving gene prediction accuracy.

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Cellular Pathway Mapping with Gene Expression Profiles & Regulatory Elements by Melanie Smith

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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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