synthetic lethal interactions in yeast
DESCRIPTION
A paper talk:Qi Y, Suhail Y, Lin YY, Boeke JD, Bader JS. Finding friends and enemies in an enemies-only network: a graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions. Genome Res. 2008 Dec;18(12):1991-2004.TRANSCRIPT
- 1. Learning of Synthetic Lethal Interactions in Yeast
2. ROD at CISBAN
- Yeast High-Throughput experiments on ageing
- Semi-automated
- Robot Object Database to track strains through multiple experiments
3. Synthetic Lethality
- Telomere uncapping
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- CDC13-1
- Double deletions
- Drug interactions
- Can we predict it?
4. Friends and Enemies Network
- Implement paper:
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- Qi Y, Suhail Y, Lin YY, Boeke JD, Bader JS. Finding friends and enemies in an enemies-only network: a graph diffusion kernel for predicting novel genetic interactions and co-complex membership from yeast genetic interactions. Genome Res. 2008 Dec;18(12):1991-2004.
5. Friends and Enemies 6. Gas Diffusion Network 7. Gas Diffusion Networks ij == ji i j 8. Gas Diffusion Networks 9. 1 1 2 3 4 5 2 3 3 4 5 5 Gas Diffusion Networks 10. 1 1 2 3 4 5 2 3 3 4 5 5 Same pathway? 11. 1 1 2 3 4 5 2 3 3 4 5 5 Same pathway? 12. 1 1 2 3 4 5 2 3 3 4 5 5 Different pathways? 13. 1 1 2 3 4 5 2 3 3 4 5 5 Different pathways? 14. 1 1 2 3 4 5 2 3 3 4 5 5 Different Pathways? 15. 16. Kernel Methods
- Similar to Support Vector Machines
- Compare all nodes to all other nodes and assign a numerical comparison
- In this case, the reachability from each node to every other node in the graph
17. Some squiggles
- G- : the reachability using odd length paths
- G+ : the reachability of even length paths
- G is the reachability of all path lengths
18. Experimental confirmation
- Gene: ADA2
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- Transcriptional co-activator in histone acetylation
- Used G- with synthetic lethal and synthetic sick from BioGRID
- Additional known positives may be found further down the ranked list
19. 20. True Positives 21. False Positives - Orange 22. False Negatives 23. Results
- 48 True Positives
- 52 False Positives
- 45 False Negatives
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- 12 not in BioGRID
24. Re-implementation
- BioGrid 2.0.27
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- Total yeast interactions:
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- Them: 18 492
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- Me: 18 505
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- Yeast interactions after removing duplicates and singletons
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- Them: 13 022
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- Me: 13 913
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- Used their query gene ADA2
25. Problems
- Some genes had different names
- No hits!
- Email to author: Please check your methods and try again
26. Future Work
- Given up on paper
- Could be potential in gas diffusion methods
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- Cedric's resistance-based method
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- Possible collaboration with Daniel Ashlock