Combining sequence motifs and protein interactions to unravel complex phosphorylation networks

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Analysis of complex biological systems, Shanghai Jiao Tong University, Shanghai, China, August 19, 2009.

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Combining sequence motifs and protein interactions to unravel complex phosphorylation networks

  1. 1. Combining sequence motifs and protein interactions to unravel complex phosphorylation networks Lars Juhl Jensen
  2. 2. the problem
  3. 3. phosphoproteomics
  4. 4. Linding, Jensen, Ostheimer et al., Cell , 2007
  5. 5. in vivo phosphosites
  6. 6. kinases are unknown
  7. 7. functions are unknown
  8. 8. sequence specificity
  9. 9. peptide assays
  10. 10. Miller, Jensen et al., Science Signaling , 2008
  11. 11. domain-specific
  12. 12. in vitro
  13. 13. no context
  14. 14. what could happen
  15. 15. not what does happen
  16. 16. machine-learning methods
  17. 17. sequence motifs
  18. 18. Miller, Jensen et al., Science Signaling , 2008
  19. 19. domain-specific
  20. 20. group-specific
  21. 21. no context
  22. 22. what could happen
  23. 23. not what does happen
  24. 24. in vitro
  25. 25. in vivo
  26. 26. context
  27. 27. co-activators
  28. 28. protein scaffolds
  29. 29. subcellular localization
  30. 30. spatial expression
  31. 31. temporal expression
  32. 32. association networks
  33. 33. Linding, Jensen, Ostheimer et al., Cell , 2007
  34. 34. the idea
  35. 35. Linding, Jensen, Ostheimer et al., Cell , 2007
  36. 36. the sequence motifs
  37. 37. NetPhorest
  38. 38. automated pipeline
  39. 39. Miller, Jensen et al., Science Signaling , 2008
  40. 40. data organization
  41. 41. Miller, Jensen et al., Science Signaling , 2008
  42. 42. compilation of datasets
  43. 43. redundancy reduction
  44. 44. training and evaluation
  45. 45. classifier selection
  46. 46. motif atlas
  47. 48. 179 kinases
  48. 49. 89 SH2 domains
  49. 50. 8 PTB domains
  50. 51. BRCT domains
  51. 52. WW domains
  52. 53. 14-3-3 proteins
  53. 54. use cases
  54. 55. Miller, Jensen et al., Science Signaling , 2008
  55. 56. the context network
  56. 57. NetworKIN
  57. 58. Linding, Jensen, Ostheimer et al., Cell , 2007
  58. 59. STRING
  59. 60. Jensen, Kuhn et al., Nucleic Acids Research , 2009
  60. 61. protein interactions
  61. 62. Jensen & Bork, Science , 2008
  62. 63. gene coexpression
  63. 65. localization
  64. 66. Linding, Jensen, Ostheimer et al., Cell , 2007
  65. 67. benchmarking
  66. 68. Phospho.ELM
  67. 69. Linding, Jensen, Ostheimer et al., Cell , 2007
  68. 70. 2.5-fold better accuracy
  69. 71. the experiments
  70. 72. ATM signaling
  71. 73. Linding, Jensen, Ostheimer et al., Cell , 2007
  72. 74. Linding, Jensen, Ostheimer et al., Cell , 2007
  73. 75. small-scale validation
  74. 76. ATM phosphorylates Rad50
  75. 77. Linding, Jensen, Ostheimer et al., Cell , 2007
  76. 78. high-throughput validation
  77. 79. multiple reaction monitoring
  78. 80. Linding, Jensen, Ostheimer et al., Cell , 2007
  79. 81. the future
  80. 82. new scoring scheme
  81. 83. two separate scores
  82. 84. one combined score
  83. 85. path length penalty
  84. 86. model organisms
  85. 87. S. cerevisiae
  86. 88. D. melanogaster
  87. 89. C. elegans
  88. 90. ( S. pombe )
  89. 91. other modifications
  90. 92. phosphatases
  91. 93. ubiquitylation
  92. 94. F-box proteins
  93. 95. acetylation
  94. 96. Acknowledgments <ul><li>NetPhorest.info </li></ul><ul><ul><li>Rune Linding </li></ul></ul><ul><ul><li>Martin Lee Miller </li></ul></ul><ul><ul><li>Francesca Diella </li></ul></ul><ul><ul><li>Claus Jørgensen </li></ul></ul><ul><ul><li>Michele Tinti </li></ul></ul><ul><ul><li>Lei Li </li></ul></ul><ul><ul><li>Marilyn Hsiung </li></ul></ul><ul><ul><li>Sirlester A. Parker </li></ul></ul><ul><ul><li>Jennifer Bordeaux </li></ul></ul><ul><ul><li>Thomas Sicheritz-Pontén </li></ul></ul><ul><ul><li>Marina Olhovsky </li></ul></ul><ul><ul><li>Adrian Pasculescu </li></ul></ul><ul><ul><li>Jes Alexander </li></ul></ul><ul><ul><li>Stefan Knapp </li></ul></ul><ul><ul><li>Nikolaj Blom </li></ul></ul><ul><ul><li>Peer Bork </li></ul></ul><ul><ul><li>Shawn Li </li></ul></ul><ul><ul><li>Gianni Cesareni </li></ul></ul><ul><ul><li>Tony Pawson </li></ul></ul><ul><ul><li>Benjamin E. Turk </li></ul></ul><ul><ul><li>Michael B. Yaffe </li></ul></ul><ul><ul><li>Søren Brunak </li></ul></ul><ul><li>STRING.embl.de </li></ul><ul><ul><li>Christian von Mering </li></ul></ul><ul><ul><li>Michael Kuhn </li></ul></ul><ul><ul><li>Manuel Stark </li></ul></ul><ul><ul><li>Samuel Chaffron </li></ul></ul><ul><ul><li>Chris Creevey </li></ul></ul><ul><ul><li>Jean Muller </li></ul></ul><ul><ul><li>Tobias Doerks </li></ul></ul><ul><ul><li>Philippe Julien </li></ul></ul><ul><ul><li>Alexander Roth </li></ul></ul><ul><ul><li>Milan Simonovic </li></ul></ul><ul><ul><li>Jan Korbel </li></ul></ul><ul><ul><li>Berend Snel </li></ul></ul><ul><ul><li>Martijn Huynen </li></ul></ul><ul><ul><li>Peer Bork </li></ul></ul><ul><li>NetworKIN.info </li></ul><ul><ul><li>Rune Linding </li></ul></ul><ul><ul><li>Gerard Ostheimer </li></ul></ul><ul><ul><li>Heiko Horn </li></ul></ul><ul><ul><li>Martin Lee Miller </li></ul></ul><ul><ul><li>Francesca Diella </li></ul></ul><ul><ul><li>Karen Colwill </li></ul></ul><ul><ul><li>Jing Jin </li></ul></ul><ul><ul><li>Pavel Metalnikov </li></ul></ul><ul><ul><li>Vivian Nguyen </li></ul></ul><ul><ul><li>Adrian Pasculescu </li></ul></ul><ul><ul><li>Jin Gyoon Park </li></ul></ul><ul><ul><li>Leona D. Samson </li></ul></ul><ul><ul><li>Rob Russell </li></ul></ul><ul><ul><li>Peer Bork </li></ul></ul><ul><ul><li>Michael Yaffe </li></ul></ul><ul><ul><li>Tony Pawson </li></ul></ul>
  95. 97. larsjuhljensen
  96. 98. Thank you

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