Using side effects for drug target identification

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Using side effects for drug target identification

  1. 1. Using side effects for drug target identification Lars Juhl Jensen
  2. 2. the problem
  3. 3. new uses for old drugs
  4. 4. drug–drug network
  5. 5. shared target(s)
  6. 6. chemical similarity
  7. 7. Campillos & Kuhn et al., Science , 2008
  8. 8. Campillos & Kuhn et al., Science , 2008
  9. 9. similar drugs share targets
  10. 10. only trivial predictions
  11. 11. the idea
  12. 12. chemical perturbations
  13. 13. phenotypic readouts
  14. 14. drug treatment
  15. 15. side effects
  16. 16. the hard work
  17. 17. information on side effects
  18. 18. no database
  19. 19. package inserts
  20. 20. Campillos & Kuhn et al., Science , 2008
  21. 21. text mining
  22. 22. side-effect ontology
  23. 23. backtracking
  24. 24. Campillos & Kuhn et al., Science , 2008
  25. 25. manual validation
  26. 26. SIDER Kuhn et al., Molecular Systems Biology , 2010
  27. 27. side-effect correlations
  28. 28. Campillos & Kuhn et al., Science , 2008
  29. 29. GSC weighting
  30. 30. side-effect frequencies
  31. 31. Campillos & Kuhn et al., Science , 2008
  32. 32. raw similarity score
  33. 33. Campillos & Kuhn et al., Science , 2008
  34. 34. p-values
  35. 35. Campillos & Kuhn et al., Science , 2008
  36. 36. side-effect similarity
  37. 37. chemical similarity
  38. 38. Campillos & Kuhn et al., Science , 2008
  39. 39. confidence scores
  40. 40. reference set
  41. 41. incomplete databases
  42. 42. text mining
  43. 43. manual validation
  44. 44. MATADOR Günther et al., Nucleic Acids Research , 2008
  45. 45. Campillos & Kuhn et al., Science , 2008
  46. 46. the results
  47. 47. drug–drug network
  48. 48. Campillos & Kuhn et al., Science , 2008
  49. 49. categorization
  50. 50. Campillos & Kuhn et al., Science , 2008
  51. 51. 20 drug–drug pairs
  52. 52. in vitro binding assays
  53. 53. K i <10 µM for 11 of 20
  54. 54. cell assays
  55. 55. 9 of 9 showed activity
  56. 56. the future
  57. 57. link side-effects to targets
  58. 58. direct target prediction
  59. 59. Acknowledgments <ul><ul><li>Monica Campillos </li></ul></ul><ul><ul><li>Michael Kuhn </li></ul></ul><ul><ul><li>Anne-Claude Gavin </li></ul></ul><ul><ul><li>Peer Bork </li></ul></ul>
  60. 60. larsjuhljensen

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