Integration of heterogeneous data

1. Lars Juhl Jensen Integration of heterogeneous data

6. what went wrong?

7. a good question

8. signaling networks

9. Oda & Kitano, Molecular Systems Biology , 2006

10. long way to go

11. mass spectrometry

12. Linding, Jensen, Ostheimer et al., Cell , 2007

13. phosphorylation sites

14. in vivo

15. kinases are unknown

16. peptide assays

17. Miller, Jensen et al., Science Signaling , 2008

18. sequence specificity

19. kinase-specific

20. in vitro

21. no context

22. what a kinase could do

23. not what it actually does

24. computational methods

25. sequence specificity

27. kinase-specific

28. no context

29. what a kinase could do

30. not what it actually does

31. in vitro

32. in vivo

33. context

34. co-activators

35. scaffolders

36. expression

37. association networks

39. a good idea

41. Part I sequence motifs

42. curated motifs

43. PROSITE

44. ELM

45. HPRD

46. regular expressions

47. [ST]P.[KR]

48. no score

50. insufficient

51. machine learning

52. NetPhosK

53. PredPhospho

54. PHOSITE

55. GPS

56. KinasePhos

57. PPSP

58. GANNPhos

59. PhoScan

60. no regular updates

61. NetPhorest

63. data sources

64. Phospho.ELM

65. Diella et al., Nucleic Acids Res. , 2008

66. Diella et al., Nucleic Acids Res. , 2008

67. Scansite

68. Obenauer et al., Nucleic Acids Res. , 2003

70. common basis

72. automated pipeline

73. compilation of datasets

74. classification vs. prediction

76. homology reduction

78. training and evaluation

79. cross-validation

81. classifier selection

83. motif atlas

85. 179 kinases

86. 93 SH2 domains

87. 8 PTB domains

88. BRCT domains

89. WW domains

90. 14-3-3 proteins

91. phosphatases

92. model organisms

93. S. cerevisiae

94. D. melanogaster

95. C. elegans

96. biological insights

97. docking domains

99. disease-related kinases

101. predictive power

102. ROC curves

104. comparison

106. conclusions

107. data collection

108. automation

109. benchmarking

110. homology reduction!

111. Part II association networks

112. STRING

113. Jensen, Kuhn et al., Nucleic Acids Research , 2009

114. functional associations

115. data integration

116. common basis

117. 630 genomes

118. model organism databases

119. Ensembl

120. RefSeq

121. genomic context methods

122. gene fusion

123. Korbel et al., Nature Biotechnology , 2004

124. conserved neighborhood

125. operons

127. bidirectional promoters

129. phylogenetic profiles

131. primary experimental data

132. protein interactions

133. yeast two-hybrid

134. affinity purification

135. fragment complementation

136. Jensen & Bork, Science , 2008

137. genetic interactions

138. Beyer et al., Nature Reviews Genetics , 2007

139. BIND Biomolecular Interaction Network Database

140. BioGRID General Repository for Interaction Datasets

141. DIP Database of Interacting Proteins

142. IntAct

143. MINT Molecular Interactions Database

144. HPRD Human Protein Reference Database

145. PDB Protein Data Bank

146. inferred associations

147. gene coexpression

149. GEO Gene Expression Omnibus

150. expression compendia

151. curated knowledge

152. complexes

153. MIPS Munich Information center for Protein Sequences

154. Gene Ontology

155. pathways

156. Letunic & Bork, Trends in Biochemical Sciences , 2008

157. KEGG Kyoto Encyclopedia of Genes and Genomes

158. MetaCyc

159. Reactome

160. PID NCI-Nature Pathway Interaction Database

161. literature mining

162. M EDLINE

163. SGD Saccharomyces Genome Database

164. The Interactive Fly

165. OMIM Online Mendelian Inheritance in Man

166. co-mentioning

167. statistical methods

168. NLP Natural Language Processing

171. easy in theory …

172. … but not in practice

173. different formats

174. parsers

175. different identifiers

176. thesaurus

177. redundant sources

178. book keeping

179. variable quality

180. raw quality scores

181. reproducibility

182. von Mering et al., Nucleic Acids Research , 2005

183. benchmarking

185. spread over 630 genomes

186. transfer by orthology

188. two modes

189. COG mode

191. protein mode

193. combine all evidence

194. visualize

195. Frishman et al., Modern Genome Annotation , 2009

196. STITCH

198. metabolite–enzyme links

199. pathway databases

200. Letunic & Bork, Trends in Biochemical Sciences , 2008

201. drug–target links

202. Drugbank

203. PDSP K i

204. MATADOR

205. Campillos & Kuhn et al., Science , 2008

206. chemical–chemical links

207. shared targets

208. fingerprint similarity

209. chemical–protein network

211. conclusions

212. more data is better

213. quality scores

214. benchmarking

215. cross-species integration

216. Part III putting it all together

218. NetworKIN

220. benchmarking

222. 2.5-fold better accuracy

223. context is crucial

224. localization

226. DNA damage response

229. small-scale validation

230. ATM phosphorylates Rad50

232. Cdk1 phosphorylates 53BP1

234. high-throughput validation

235. multiple reaction monitoring

237. systematic validation

238. kinase inhibitor matrix

239. Fedorov et al., PNAS , 2007

240. design optimal experiments

241. integration with literature

242. Reflect

246. conclusions

247. complementary data

248. visualization

249. a good question

Integration of heterogeneous data

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Integration of heterogeneous data