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Identifying new genes involved in the DNA damage checkpoint pathway

Identifying new genes involved in the DNA damage checkpoint pathway. Courtney Onodera March 16, 2005. Overview of pathway. http://biochem.wustl.edu/~burgersw3/checkpointtxt.htm. Motivation. Lokey lab - cancer research (therapeutics) Wet lab experiments: Knock out genes with RNAi

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Identifying new genes involved in the DNA damage checkpoint pathway

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  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: • Known DNA damage checkpoint genes • Genes most sensitive to camptothecin • 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

  11. 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

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

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