Unraveling signal transduction networks through data integration

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Minisymposium on Glycoanalysis and Glycochemistry, University of Copenhagen, Copenhagen, Denmark, October 26, 2009.

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  • Atlas of human kinases Atlases for phospho-binding proteins Atlases for model organisms Ubiquitination would be welcome
  • Unraveling signal transduction networks through data integration

    1. 1. Unraveling signal transduction networks through data integration 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. guilt by association
    57. 59. STRING
    58. 60. Jensen, Kuhn et al., Nucleic Acids Research , 2009
    59. 61. functional associations
    60. 62. data integration
    61. 63. primary experimental data
    62. 64. protein interactions
    63. 65. Jensen & Bork, Science , 2008
    64. 66. gene coexpression
    65. 68. genomic context methods
    66. 69. Korbel et al., Nature Biotechnology , 2004
    67. 70. Korbel et al., Nature Biotechnology , 2004
    68. 71. literature mining
    69. 73. curated knowledge
    70. 74. Letunic & Bork, Trends in Biochemical Sciences , 2008
    71. 75. too easy …
    72. 76. … to be true
    73. 77. different formats
    74. 78. different identifiers
    75. 79. variable quality
    76. 80. spread over 630 genomes
    77. 81. parsers
    78. 82. thesaurus
    79. 83. raw quality scores
    80. 84. benchmarking
    81. 85. von Mering et al., Nucleic Acids Research , 2005
    82. 86. transfer by orthology
    83. 87. von Mering et al., Nucleic Acids Research , 2005
    84. 88. combine all evidence
    85. 89. context network
    86. 90. Linding, Jensen, Ostheimer et al., Cell , 2007
    87. 91. the results
    88. 92. NetworKIN
    89. 93. Linding, Jensen, Ostheimer et al., Cell , 2007
    90. 94. benchmarking
    91. 95. Phospho.ELM
    92. 96. Linding, Jensen, Ostheimer et al., Cell , 2007
    93. 97. context is crucial
    94. 98. much context still missing
    95. 99. subcellular localization
    96. 100. Linding, Jensen, Ostheimer et al., Cell , 2007
    97. 101. ATM signaling
    98. 102. Linding, Jensen, Ostheimer et al., Cell , 2007
    99. 103. small-scale validation
    100. 104. ATM phosphorylates Rad50
    101. 105. Linding, Jensen, Ostheimer et al., Cell , 2007
    102. 106. Cdk1 phosphorylates 53BP1
    103. 107. Linding, Jensen, Ostheimer et al., Cell , 2007
    104. 108. high-throughput validation
    105. 109. multiple reaction monitoring
    106. 110. Linding, Jensen, Ostheimer et al., Cell , 2007
    107. 111. the future
    108. 112. new scoring scheme
    109. 113. two separate scores
    110. 114. one combined score
    111. 115. path length penalty
    112. 116. model organisms
    113. 117. S. cerevisiae
    114. 118. D. melanogaster
    115. 119. C. elegans
    116. 120. ( S. pombe )
    117. 121. other modifications
    118. 122. phosphatases
    119. 123. ubiquitylation
    120. 124. acetylation
    121. 125. glycosylation
    122. 126. 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-DB.org </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 B. Yaffe </li></ul></ul><ul><ul><li>Tony Pawson </li></ul></ul>
    123. 127. larsjuhljensen

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