Data Integration and Systems Biology

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Danish Protein Science Meeting, Skt. Helene, Tisvildeleje, Denmark, November 6-7, 2008

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Data Integration and Systems Biology

  1. 1. Lars Juhl Jensen Data Integration and Systems Biology
  2. 2. Lars Juhl Jensen Data Integration and Systems Biology
  3. 3. what went wrong?
  4. 4. a good problem
  5. 5. a good idea
  6. 6. cell-cycle regulation
  7. 7. microarray data
  8. 8. interaction network
  9. 9. de Lichtenberg, Jensen, et al., Science , 2005
  10. 10. new uses for old drugs
  11. 11. chemical similarity
  12. 12. side effects
  13. 16. the problem
  14. 17. phosphorylation networks
  15. 18. mass spectrometry
  16. 19. Linding, Jensen, Ostheimer et al., Cell , 2007
  17. 20. phosphorylation sites
  18. 21. in vivo
  19. 22. kinases are unknown
  20. 23. peptide assays
  21. 24. Miller, Jensen et al., Science Signaling , 2008
  22. 25. sequence specificity
  23. 26. kinase-specific
  24. 27. in vitro
  25. 28. no context
  26. 29. what a kinase could do
  27. 30. not what it actually does
  28. 31. computational methods
  29. 32. sequence specificity
  30. 33. Miller, Jensen et al., Science Signaling , 2008
  31. 34. kinase-specific
  32. 35. no context
  33. 36. what a kinase could do
  34. 37. not what it actually does
  35. 38. in vitro
  36. 39. in vivo
  37. 40. context
  38. 41. co-activators
  39. 42. scaffolders
  40. 43. expression
  41. 44. association networks
  42. 45. Linding, Jensen, Ostheimer et al., Cell , 2007
  43. 46. the idea
  44. 47. mass spectrometry
  45. 48. phosphorylation sites
  46. 49. sequence motifs
  47. 50. sequence specificity
  48. 51. association network
  49. 52. context
  50. 53. in vitro
  51. 54. in vivo
  52. 55. Linding, Jensen, Ostheimer et al., Cell , 2007
  53. 56. the sequence motifs
  54. 57. NetPhorest
  55. 58. Miller, Jensen et al., Science Signaling , 2008
  56. 59. pipeline
  57. 60. data organization
  58. 61. Miller, Jensen et al., Science Signaling , 2008
  59. 62. compilation of datasets
  60. 63. Miller, Jensen et al., Science Signaling , 2008
  61. 64. redundancy reduction
  62. 65. Miller, Jensen et al., Science Signaling , 2008
  63. 66. cross-validation partitioning
  64. 67. Miller, Jensen et al., Science Signaling , 2008
  65. 68. training and evaluation
  66. 69. classifier selection
  67. 70. Miller, Jensen et al., Science Signaling , 2008
  68. 71. motif atlas
  69. 73. 179 kinases
  70. 74. 93 SH2 domains
  71. 75. 8 PTB domains
  72. 76. BRCT domains
  73. 77. WW domains
  74. 78. 14-3-3 proteins
  75. 79. benchmarking
  76. 80. Miller, Jensen et al., Science Signaling , 2008
  77. 81. low-specificity kinases
  78. 82. disease-related kinases
  79. 83. Miller, Jensen et al., Science Signaling , 2008
  80. 84. docking domains
  81. 85. Miller, Jensen et al., Science Signaling , 2008
  82. 86. the context network
  83. 87. STRING
  84. 88. functional associations
  85. 89. 373 genomes
  86. 90. Jensen et al., Nucleic Acids Research , 2008
  87. 91. genomic context methods
  88. 92. gene fusion
  89. 93. Korbel et al., Nature Biotechnology , 2004
  90. 94. conserved neighborhood
  91. 95. Korbel et al., Nature Biotechnology , 2004
  92. 96. phylogenetic profiles
  93. 97. Korbel et al., Nature Biotechnology , 2004
  94. 98. primary experimental data
  95. 99. protein interactions
  96. 100. Jensen & Bork, Science , 2008
  97. 101. gene coexpression
  98. 103. literature mining
  99. 105. curated knowledge
  100. 106. Letunic & Bork, Trends in Biochemical Sciences , 2008
  101. 107. different formats
  102. 108. parsers
  103. 109. different gene identifiers
  104. 110. thesaurus
  105. 111. redundancy
  106. 112. bookkeeping
  107. 113. variable reliability
  108. 114. benchmarking
  109. 115. von Mering et al., Nucleic Acids Research , 2005
  110. 116. spread over many species
  111. 117. transfer by orthology
  112. 118. von Mering et al., Nucleic Acids Research , 2005
  113. 119. combine all evidence
  114. 120. Linding, Jensen, Ostheimer et al., Cell , 2007
  115. 121. the results
  116. 122. NetworKIN
  117. 123. 123 kinases
  118. 124. 5515 substrates
  119. 125. 21,702 sites
  120. 126. benchmarking
  121. 127. Phospho.ELM
  122. 128. Linding, Jensen, Ostheimer et al., Cell , 2007
  123. 129. 2.5-fold better accuracy
  124. 130. context is crucial
  125. 131. ATM signaling
  126. 132. Linding, Jensen, Ostheimer et al., Cell , 2007
  127. 133. Linding, Jensen, Ostheimer et al., Cell , 2007
  128. 134. small-scale validation
  129. 135. ATM phosphorylates Rad50
  130. 136. Linding, Jensen, Ostheimer et al., Cell , 2007
  131. 137. high-throughput validation
  132. 138. multiple reaction monitoring
  133. 139. Linding, Jensen, Ostheimer et al., Cell , 2007
  134. 140. systematic validation
  135. 141. kinase inhibitor matrix
  136. 142. Fedorov et al., PNAS , 2007
  137. 143. design optimal experiments
  138. 144. 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>
  139. 145. http://larsjuhljensen.wordpress.com

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