Unraveling cellular phosphorylation networks using computational biology

967 views

Published on

BRIC/LEO Minisymposium on Protein Kinases in Health and Disease, Copenhagen Biocenter, Copenhagen, September 26, 2008

Published in: Technology
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
967
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
12
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Unraveling cellular phosphorylation networks using computational biology

  1. 1. Unraveling cellular phosphorylation networks using computational biology Lars Juhl Jensen EMBL Heidelberg
  2. 2. the problem
  3. 3. Oda & Kitano, Molecular Systems Biology , 2006
  4. 4. a good start
  5. 5. long way to go
  6. 6. the toolbox
  7. 7. mass spectrometry
  8. 8. Linding, Jensen, Ostheimer et al., Cell , 2007
  9. 9. phosphorylation sites
  10. 10. in vivo
  11. 11. kinases are unknown
  12. 12. peptide assays
  13. 13. Miller, Jensen et al., Science Signaling , 2008
  14. 14. sequence specificity
  15. 15. kinase-specific
  16. 16. in vitro
  17. 17. no context
  18. 18. what a kinase could do
  19. 19. not what it actually does
  20. 20. computational methods
  21. 21. sequence specificity
  22. 22. Miller, Jensen et al., Science Signaling , 2008
  23. 23. kinase-specific
  24. 24. no context
  25. 25. what a kinase could do
  26. 26. not what it actually does
  27. 27. in vitro
  28. 28. in vivo
  29. 29. context
  30. 30. localization
  31. 31. expression
  32. 32. co-activators
  33. 33. scaffolders
  34. 34. association networks
  35. 35. Linding, Jensen, Ostheimer et al., Cell , 2007
  36. 36. the idea
  37. 37. mass spectrometry
  38. 38. phosphorylation sites
  39. 39. sequence motifs
  40. 40. sequence specificity
  41. 41. association network
  42. 42. context
  43. 43. in vitro
  44. 44. in vivo
  45. 45. Linding, Jensen, Ostheimer et al., Cell , 2007
  46. 46. the sequence motifs
  47. 47. NetPhorest
  48. 48. Miller, Jensen et al., Science Signaling , 2008
  49. 49. pipeline
  50. 50. data organization
  51. 51. Miller, Jensen et al., Science Signaling , 2008
  52. 52. compilation of datasets
  53. 53. Miller, Jensen et al., Science Signaling , 2008
  54. 54. redundancy reduction
  55. 55. Miller, Jensen et al., Science Signaling , 2008
  56. 56. cross-validation partitioning
  57. 57. Miller, Jensen et al., Science Signaling , 2008
  58. 58. training and evaluation
  59. 59. classifier selection
  60. 60. Miller, Jensen et al., Science Signaling , 2008
  61. 61. motif atlas
  62. 63. 179 kinases
  63. 64. 93 SH2 domains
  64. 65. 8 PTB domains
  65. 66. BRCT domains
  66. 67. WW domains
  67. 68. 14-3-3 proteins
  68. 69. benchmarking
  69. 70. Miller, Jensen et al., Science Signaling , 2008
  70. 71. low-specificity kinases
  71. 72. disease-related kinases
  72. 73. Miller, Jensen et al., Science Signaling , 2008
  73. 74. docking domains
  74. 75. Miller, Jensen et al., Science Signaling , 2008
  75. 76. the context network
  76. 77. STRING
  77. 78. functional associations
  78. 79. 373 genomes
  79. 80. Jensen et al., Nucleic Acids Research , 2008
  80. 81. genomic context methods
  81. 82. gene fusion
  82. 83. Korbel et al., Nature Biotechnology , 2004
  83. 84. conserved neighborhood
  84. 85. Korbel et al., Nature Biotechnology , 2004
  85. 86. phylogenetic profiles
  86. 87. Korbel et al., Nature Biotechnology , 2004
  87. 88. primary experimental data
  88. 89. protein interactions
  89. 90. Jensen & Bork, Science , 2008
  90. 91. gene coexpression
  91. 93. literature mining
  92. 95. curated knowledge
  93. 96. Letunic & Bork, Trends in Biochemical Sciences , 2008
  94. 97. different formats
  95. 98. parsers
  96. 99. different gene identifiers
  97. 100. thesaurus
  98. 101. redundancy
  99. 102. bookkeeping
  100. 103. variable reliability
  101. 104. benchmarking
  102. 105. von Mering et al., Nucleic Acids Research , 2005
  103. 106. spread over many species
  104. 107. transfer by orthology
  105. 108. von Mering et al., Nucleic Acids Research , 2005
  106. 109. combine all evidence
  107. 110. Linding, Jensen, Ostheimer et al., Cell , 2007
  108. 111. the results
  109. 112. NetworKIN
  110. 113. 123 kinases
  111. 114. 5515 substrates
  112. 115. 21,702 sites
  113. 116. benchmarking
  114. 117. Phospho.ELM
  115. 118. Linding, Jensen, Ostheimer et al., Cell , 2007
  116. 119. 2.5-fold better accuracy
  117. 120. context is crucial
  118. 121. localization
  119. 122. Linding, Jensen, Ostheimer et al., Cell , 2007
  120. 123. ATM signaling
  121. 124. Linding, Jensen, Ostheimer et al., Cell , 2007
  122. 125. Linding, Jensen, Ostheimer et al., Cell , 2007
  123. 126. small-scale validation
  124. 127. ATM phosphorylates Rad50
  125. 128. Linding, Jensen, Ostheimer et al., Cell , 2007
  126. 129. Cdk1 phosphorylates 53BP1
  127. 130. Linding, Jensen, Ostheimer et al., Cell , 2007
  128. 131. high-throughput validation
  129. 132. multiple reaction monitoring
  130. 133. Linding, Jensen, Ostheimer et al., Cell , 2007
  131. 134. systematic validation
  132. 135. design optimal experiments
  133. 136. Acknowledgments <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>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><ul><li>NetPhorest.info </li></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>Philippe Julien </li></ul></ul><ul><ul><li>Tobias Doerks </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>
  134. 137. Want to work on this project?

×