Unraveling signaling networks by large-scale data integration

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BioRange, Lunteren, Netherlands, March 17-18, 2009

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Unraveling signaling networks by large-scale data integration

  1. 1. Unraveling signaling networks by large-scale data integration Lars Juhl Jensen
  2. 6. the problem
  3. 7. phosphoproteomics
  4. 8. Linding, Jensen, Ostheimer et al., Cell , 2007
  5. 9. in vivo phosphosites
  6. 10. kinases are unknown
  7. 11. peptide assays
  8. 12. Miller, Jensen et al., Science Signaling , 2008
  9. 13. machine-learning methods
  10. 14. sequence motifs
  11. 15. Miller, Jensen et al., Science Signaling , 2008
  12. 16. kinase-specific
  13. 17. sequence specificity
  14. 18. no context
  15. 19. what a kinase could do
  16. 20. not what it actually does
  17. 21. context
  18. 22. co-activators
  19. 23. scaffolders
  20. 24. localization
  21. 25. expression
  22. 26. association networks
  23. 27. Linding, Jensen, Ostheimer et al., Cell , 2007
  24. 28. the good idea
  25. 29. Linding, Jensen, Ostheimer et al., Cell , 2007
  26. 30. a lot of work
  27. 31. the sequence motifs
  28. 32. NetPhorest
  29. 33. Miller, Jensen et al., Science Signaling , 2008
  30. 34. data organization
  31. 35. Miller, Jensen et al., Science Signaling , 2008
  32. 36. automated pipeline
  33. 37. compilation of datasets
  34. 38. redundancy reduction
  35. 39. training and evaluation
  36. 40. classifier selection
  37. 41. motif atlas
  38. 43. 179 kinases
  39. 44. 93 SH2 domains
  40. 45. 8 PTB domains
  41. 46. BRCT domains
  42. 47. WW domains
  43. 48. 14-3-3 proteins
  44. 49. phosphatases
  45. 50. model organisms
  46. 51. biological insights
  47. 52. docking domains
  48. 53. Miller, Jensen et al., Science Signaling , 2008
  49. 54. disease-related kinases
  50. 55. Miller, Jensen et al., Science Signaling , 2008
  51. 56. the context network
  52. 57. STRING
  53. 58. Jensen, Kuhn et al., Nucleic Acids Research , 2009
  54. 59. functional associations
  55. 60. data integration
  56. 61. primary experimental data
  57. 62. protein interactions
  58. 63. Jensen & Bork, Science , 2008
  59. 64. gene coexpression
  60. 66. genomic context methods
  61. 67. gene fusion
  62. 68. Korbel et al., Nature Biotechnology , 2004
  63. 69. conserved neighborhood
  64. 70. Korbel et al., Nature Biotechnology , 2004
  65. 71. literature mining
  66. 73. curated knowledge
  67. 74. Letunic & Bork, Trends in Biochemical Sciences , 2008
  68. 75. too easy …
  69. 76. … to be true
  70. 77. different formats
  71. 78. different identifiers
  72. 79. variable quality
  73. 80. spread over 630 genomes
  74. 81. parsers
  75. 82. thesaurus
  76. 83. raw quality scores
  77. 84. benchmarking
  78. 85. von Mering et al., Nucleic Acids Research , 2005
  79. 86. transfer by orthology
  80. 87. von Mering et al., Nucleic Acids Research , 2005
  81. 88. combine all evidence
  82. 89. visualize
  83. 90. Frishman et al., Modern Genome Annotation , 2009
  84. 91. the results
  85. 92. NetworKIN
  86. 94. benchmarking
  87. 95. Linding, Jensen, Ostheimer et al., Cell , 2007
  88. 96. DNA damage response
  89. 97. Linding, Jensen, Ostheimer et al., Cell , 2007
  90. 98. small-scale validation
  91. 99. ATM phosphorylates Rad50
  92. 100. Linding, Jensen, Ostheimer et al., Cell , 2007
  93. 101. high-throughput validation
  94. 102. multiple reaction monitoring
  95. 103. Linding, Jensen, Ostheimer et al., Cell , 2007
  96. 104. 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>

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