1. Pathways Analysis using Protein Expression Data Venkatesh Jitender (vjk@cbmi.upmc.edu) Dr. Vanathi Gopalakrishnan Center for Biomedical Informatics, UPMC

2. Bio-Chemical Pathways & Protein Expression Profiles Organisms function through intricate networks of chemical reactions and interacting molecules. Metabolic Pathway Can be thought of as a “state representation” network Regulatory Pathway: Can be thought of as a “switch activating or de-activating” diagram Protein Expression Profiles: Mass- spectrometry Protein Array technology, etc.

3. KEGG Database: Suite of Databases and Associated Software http://www.genome.ad.jp/kegg/kegg2.html#pathway Includes : PATHWAY database GENES & PROTEINS (Genes / SSD / KO databases) CHEMICAL COMPOUNDS & REACTIONS (Compound / Reaction database ) Statistics: Number of pathways10,677(PATHWAY database) Number of reference pathways226(PATHWAY database)

4. Metabolic Pathway:

5. Regulatory Pathway:

6. Proposal: Identify co- relation between observed protein expression profiles and Biochemical Pathways. Provide an online web-service to predict the “Most-Probable” pathway Rank putative pathways based on Activity score: analyze difference in expression profiles Co regulation score: analyze similarity in expression profiles within a pathway Cascade score: analyze structure, measuring activity and coregulation

7. User submits sequence data get_pathway_by_enzyme Putative Pathway Set KEGG Server KEGG API Recommended Pathway Analysis Routine Application Server Project Architecture

8. Putative Pathway Set Suggested Pathway Analysis Routine Application Server Analysis Routine Score Pathway based on: Activity Coregulation Cascade

9. Implementation Details Option of program being hosted public (server) / standalone application Application server: JAVA servlets, JSP Analysis Routine: C/ JAVA Messaging System: HTTP Communication Protocol: SOAP (xml format)

10. Applications: Pathway knowledge helpful in: Deeper understanding of cell mechanisms under various conditions Predict possible drug targets, Provide end- user on most probable pathway set, from a publicly available database