From phosphoproteomics to signaling networks Lars Juhl Jensen
 
 
 
 
Orbitrap
 
in vivo  phosphosites
kinases are unknown
functions are unknown
sequence motifs
machine-learning methods
Miller, Jensen et al.,  Science Signaling , 2008
peptide assays
Miller, Jensen et al.,  Science Signaling , 2008
domain-specific
group-specific
no context
in vitro
in vivo
context
co-activators
protein scaffolds
localization
expression
NetworKIN
Linding, Jensen, Ostheimer et al.,  Cell , 2007
functional associations
Jensen, Kuhn et al.,  Nucleic Acids Research , 2009
data integration
pathways
Letunic & Bork,  Trends in Biochemical Sciences , 2008
protein interactions
Jensen & Bork,  Science , 2008
gene coexpression
 
genomic context methods
Korbel et al.,  Nature Biotechnology , 2004
literature mining
 
different formats
different identifiers
variable quality
not comparable
spread over 630 genomes
confidence scores
von Mering et al.,  Nucleic Acids Research , 2005
transfer by orthology
von Mering et al.,  Nucleic Acids Research , 2005
Linding, Jensen, Ostheimer et al.,  Cell , 2007
does it work?
Linding, Jensen, Ostheimer et al.,  Cell , 2007
context is crucial
much context missing
many motifs missing
NetPhorest
automated pipeline
Miller, Jensen et al.,  Science Signaling , 2008
data organization
Miller, Jensen et al.,  Science Signaling , 2008
compilation of datasets
redundancy reduction
training and evaluation
classifier selection
motif atlas
 
179 kinases
89 SH2 domains
8 PTB domains
BRCT domains
WW domains
14-3-3 proteins
use case
cell-cycle kinases
Olsen et al.,  Science Signaling , 2009
coming soon(ish)
new web interface
new scoring scheme
path length penalty
Linding, Jensen, Ostheimer et al.,  Cell , 2007
model organisms
S. cerevisiae
D. melanogaster
C. elegans
other modifications
phosphatases
acetylation
ubiquitylation
Acknowledgments <ul><li>NetPhorest.info </li></ul><ul><ul><li>Rune Linding </li></ul></ul><ul><ul><li>Martin Lee Miller </...
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From phosphoproteomics to signaling networks

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Orbitrap User Meeting, University of Southern Denmark, Odense, Denmark, December 2, 2009.

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  • Integration Automation Collaboration
  • Atlas of human kinases Atlases for phospho-binding proteins Atlases for model organisms Ubiquitination would be welcome
  • From phosphoproteomics to signaling networks

    1. 1. From phosphoproteomics to signaling networks Lars Juhl Jensen
    2. 6. Orbitrap
    3. 8. in vivo phosphosites
    4. 9. kinases are unknown
    5. 10. functions are unknown
    6. 11. sequence motifs
    7. 12. machine-learning methods
    8. 13. Miller, Jensen et al., Science Signaling , 2008
    9. 14. peptide assays
    10. 15. Miller, Jensen et al., Science Signaling , 2008
    11. 16. domain-specific
    12. 17. group-specific
    13. 18. no context
    14. 19. in vitro
    15. 20. in vivo
    16. 21. context
    17. 22. co-activators
    18. 23. protein scaffolds
    19. 24. localization
    20. 25. expression
    21. 26. NetworKIN
    22. 27. Linding, Jensen, Ostheimer et al., Cell , 2007
    23. 28. functional associations
    24. 29. Jensen, Kuhn et al., Nucleic Acids Research , 2009
    25. 30. data integration
    26. 31. pathways
    27. 32. Letunic & Bork, Trends in Biochemical Sciences , 2008
    28. 33. protein interactions
    29. 34. Jensen & Bork, Science , 2008
    30. 35. gene coexpression
    31. 37. genomic context methods
    32. 38. Korbel et al., Nature Biotechnology , 2004
    33. 39. literature mining
    34. 41. different formats
    35. 42. different identifiers
    36. 43. variable quality
    37. 44. not comparable
    38. 45. spread over 630 genomes
    39. 46. confidence scores
    40. 47. von Mering et al., Nucleic Acids Research , 2005
    41. 48. transfer by orthology
    42. 49. von Mering et al., Nucleic Acids Research , 2005
    43. 50. Linding, Jensen, Ostheimer et al., Cell , 2007
    44. 51. does it work?
    45. 52. Linding, Jensen, Ostheimer et al., Cell , 2007
    46. 53. context is crucial
    47. 54. much context missing
    48. 55. many motifs missing
    49. 56. NetPhorest
    50. 57. automated pipeline
    51. 58. Miller, Jensen et al., Science Signaling , 2008
    52. 59. data organization
    53. 60. Miller, Jensen et al., Science Signaling , 2008
    54. 61. compilation of datasets
    55. 62. redundancy reduction
    56. 63. training and evaluation
    57. 64. classifier selection
    58. 65. motif atlas
    59. 67. 179 kinases
    60. 68. 89 SH2 domains
    61. 69. 8 PTB domains
    62. 70. BRCT domains
    63. 71. WW domains
    64. 72. 14-3-3 proteins
    65. 73. use case
    66. 74. cell-cycle kinases
    67. 75. Olsen et al., Science Signaling , 2009
    68. 76. coming soon(ish)
    69. 77. new web interface
    70. 78. new scoring scheme
    71. 79. path length penalty
    72. 80. Linding, Jensen, Ostheimer et al., Cell , 2007
    73. 81. model organisms
    74. 82. S. cerevisiae
    75. 83. D. melanogaster
    76. 84. C. elegans
    77. 85. other modifications
    78. 86. phosphatases
    79. 87. acetylation
    80. 88. ubiquitylation
    81. 89. 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>
    82. 90. larsjuhljensen

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