Systematic discovery of phosphorylation networks Combining linear motifs and protein interactions Lars Juhl Jensen EMBL He...
Lars Juhl Jensen
 
 
promoter analysis
 
genome visualization
 
protein function prediction
 
 
 
data integration
 
dynamic interactions
 
prediction of interactions
http://string.embl.de
prediction of interactions
http://networkin.info
the starting point
phosphoproteomics
mass spectrometry
 
phosphorylation sites
in vivo
kinases are unknown
HTP kinase assays
in vitro
no context
what a kinase could do
not what it actually does
computational methods
sequence motifs
 
kinase families
phosphorylation sites
overprediction
no context
what a kinase could do
not what it actually does
in vitro
in vivo
context
localization
expression
co-activators
scaffolders
protein networks
 
the idea
mass spectrometry
 
phosphorylation sites
sequence motifs
 
kinase families
protein networks
 
context
in vitro
in vivo
“ shake and bake”
 
NetworKIN
the context network
STRING
functional interactions
373 genomes
 
genomic context methods
gene neighborhood
 
gene fusion
 
phylogenetic profiles
 
primary experimental data
protein interactions
 
genetic interactions
 
gene coexpression
 
literature mining
 
curated knowledge
 
many sources
different formats
different gene identifiers
redundancy
variable quality
spread over many species
benchmarking
 
transfer by orthology
 
combine all evidence
 
the results
 
7797 predictions
1790 substrates
69 kinases
 
benchmarking
Phospho.ELM
 
2.5-fold better accuracy
context is crucial
localization
 
visualization
 
ATM signaling
 
small-scale validation
ATM phosphorylates Rad50
 
Cdk1 phosphorylates 53BP1
 
high-throughput validation
multiple reaction monitoring
 
the future
NetPhorest
sequence motifs
in vivo
in vitro
automatic pipeline
data organization
 
benchmarking
selection
 
~200 kinases
~100 SH2 domains
~15 PTB domains
upstream signaling
downstream signaling
ordered signaling events
signaling pathways
Acknowledgments <ul><li>The NetworKIN method </li></ul><ul><ul><li>Rune Linding </li></ul></ul><ul><ul><li>Gerard Ostheime...
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Systematic discovery of phosphorylation networks - Combining linear motifs and protein interactions

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Novel approaches to study kinase and GTPase signaling, Plate-forme Génomique fonctionnelle Bordeaux Aquitaine, Bordeaux, France, September 26-28, 2007

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Systematic discovery of phosphorylation networks - Combining linear motifs and protein interactions

  1. 1. Systematic discovery of phosphorylation networks Combining linear motifs and protein interactions Lars Juhl Jensen EMBL Heidelberg
  2. 2. Lars Juhl Jensen
  3. 5. promoter analysis
  4. 7. genome visualization
  5. 9. protein function prediction
  6. 13. data integration
  7. 15. dynamic interactions
  8. 17. prediction of interactions
  9. 18. http://string.embl.de
  10. 19. prediction of interactions
  11. 20. http://networkin.info
  12. 21. the starting point
  13. 22. phosphoproteomics
  14. 23. mass spectrometry
  15. 25. phosphorylation sites
  16. 26. in vivo
  17. 27. kinases are unknown
  18. 28. HTP kinase assays
  19. 29. in vitro
  20. 30. no context
  21. 31. what a kinase could do
  22. 32. not what it actually does
  23. 33. computational methods
  24. 34. sequence motifs
  25. 36. kinase families
  26. 37. phosphorylation sites
  27. 38. overprediction
  28. 39. no context
  29. 40. what a kinase could do
  30. 41. not what it actually does
  31. 42. in vitro
  32. 43. in vivo
  33. 44. context
  34. 45. localization
  35. 46. expression
  36. 47. co-activators
  37. 48. scaffolders
  38. 49. protein networks
  39. 51. the idea
  40. 52. mass spectrometry
  41. 54. phosphorylation sites
  42. 55. sequence motifs
  43. 57. kinase families
  44. 58. protein networks
  45. 60. context
  46. 61. in vitro
  47. 62. in vivo
  48. 63. “ shake and bake”
  49. 65. NetworKIN
  50. 66. the context network
  51. 67. STRING
  52. 68. functional interactions
  53. 69. 373 genomes
  54. 71. genomic context methods
  55. 72. gene neighborhood
  56. 74. gene fusion
  57. 76. phylogenetic profiles
  58. 78. primary experimental data
  59. 79. protein interactions
  60. 81. genetic interactions
  61. 83. gene coexpression
  62. 85. literature mining
  63. 87. curated knowledge
  64. 89. many sources
  65. 90. different formats
  66. 91. different gene identifiers
  67. 92. redundancy
  68. 93. variable quality
  69. 94. spread over many species
  70. 95. benchmarking
  71. 97. transfer by orthology
  72. 99. combine all evidence
  73. 101. the results
  74. 103. 7797 predictions
  75. 104. 1790 substrates
  76. 105. 69 kinases
  77. 107. benchmarking
  78. 108. Phospho.ELM
  79. 110. 2.5-fold better accuracy
  80. 111. context is crucial
  81. 112. localization
  82. 114. visualization
  83. 116. ATM signaling
  84. 118. small-scale validation
  85. 119. ATM phosphorylates Rad50
  86. 121. Cdk1 phosphorylates 53BP1
  87. 123. high-throughput validation
  88. 124. multiple reaction monitoring
  89. 126. the future
  90. 127. NetPhorest
  91. 128. sequence motifs
  92. 129. in vivo
  93. 130. in vitro
  94. 131. automatic pipeline
  95. 132. data organization
  96. 134. benchmarking
  97. 135. selection
  98. 137. ~200 kinases
  99. 138. ~100 SH2 domains
  100. 139. ~15 PTB domains
  101. 140. upstream signaling
  102. 141. downstream signaling
  103. 142. ordered signaling events
  104. 143. signaling pathways
  105. 144. Acknowledgments <ul><li>The NetworKIN method </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>The STRING database </li></ul><ul><ul><li>Christian von Mering </li></ul></ul><ul><ul><li>Michael Kuhn </li></ul></ul><ul><ul><li>Berend Snel </li></ul></ul><ul><ul><li>Martijn Huynen </li></ul></ul><ul><ul><li>Samuel Chaffron </li></ul></ul><ul><ul><li>Peer Bork </li></ul></ul><ul><li>The NetPhorest method </li></ul><ul><ul><li>Martin Lee Miller </li></ul></ul><ul><ul><li>Rune Linding </li></ul></ul><ul><ul><li>Nikolaj Blom </li></ul></ul><ul><ul><li>Søren Brunak </li></ul></ul>

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