synthetic lethal interactions in yeast

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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
    • CDC13-1
  • Double deletions
  • Drug interactions
  • Can we predict it?

4. Friends and Enemies Network

  • Implement paper:
    • 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
    • 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
    • 12 not in BioGRID

24. Re-implementation

  • BioGrid 2.0.27
    • Total yeast interactions:
      • Them: 18 492
      • Me: 18 505
    • Yeast interactions after removing duplicates and singletons
      • Them: 13 022
      • Me: 13 913
  • 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
    • Cedric's resistance-based method
    • Possible collaboration with Daniel Ashlock