1. Identifying new genes involved in the DNA damage checkpoint pathway Courtney Onodera March 16, 2005

2. Overview of pathway http://biochem.wustl.edu/~burgersw3/checkpointtxt.htm

3. Motivation Lokey lab - cancer research (therapeutics) Wet lab experiments: –Knock out genes with RNAi –Treat cells with camptothecin (DNA damaging agent) –See if cells proceed with cell division or not

4. Stuff we had to start with List of genes known to be involved in the DNA damage checkpoint pathway (Scott, Josh, and Gene Ontology) Chemical sensitivity data from yeast (Boone Lab, UToronto) –Synthetic lethal interactions with DNA damaging agents camptothecin and hydroxyurea –Genes ranked on scale of 0-3 (not sensitive - most sensitive)

5. Strategy Start with a list of genes known to be involved in the pathway Utilize existing recommender programs to find additional candidates for the pathway Incorporate results from the different programs along with chemical sensitivity data to find the best overall candidates

6. Multi-Species Gene Recommender (MSGR) http://kolossus.cse.ucsc.edu:8001/GRJava/howitworks.html

7. Multi-species network analysis Results were a little harder to deal with… …leaving them out for now…

8. What I did Ran MSGR with queries: 1.Known DNA damage checkpoint genes 2.Genes most sensitive to camptothecin 3.Genes most sensitive to hydroxyurea Combined p-values from all tests to get an overall p-value for each gene Ranked all returned genes by overall p-value

9. Some results…

10. How to tell if my results make any sense? Look at known DNA-damage checkpoint genes returned –Rank –Total number Number of knowns returned is maximized by combining all three tests

13. Conclusion Combining the MSGR results from the three queries leads to higher sensitivity but lower precision Single query with known DNA damage checkpoint genes seems to have best combination of precision and sensitivity

14. Acknowledgements Chad Chen - MSGR Corey Powell - multi-species network Josh Stuart Scott Lokey