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Combining sequence motifs and protein interactions to unravel complex phosphorylation networks

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    Combining sequence motifs and protein interactions to unravel complex phosphorylation networks - Presentation Transcript

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