Data Integration and Systems Biology
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Data Integration and Systems Biology

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

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

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Data Integration and Systems Biology Presentation Transcript

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