University of Natural Resources and Applied Life Sciences, Vienna, Austria, February 15, 2007

1. Just-in-time assembly The evolution of transcriptional and post-translational cell-cycle regulation of protein complexes Lars Juhl Jensen EMBL Heidelberg

2. the cell cycle

3. grow and divide

4. one cell

5. two cells

6. four phases

7. G 1 phase

8. growth

9. S phase

10. DNA replication

11. G 2 phase

12. growth

13. M phase

14. cell division

16. regulation

17. gene expression

18. phosphorylation

19. targeted degradation

20. protein interactions

21. molecular biology

22. one gene

23. one postdoc

24. many types of data

25. a single gene

26. high-throughput biology

27. one lab

28. one technology

29. all the relevant genes

30. a single type of data

31. systems biology

32. many types of data

33. all the relevant genes

34. data integration

35. expression data

36. cell cultures

38. synchronization

39. microarrays

41. time courses

43. expression profiles

45. list of genes

46. periodically expressed

47. S. cerevisiae

48. expression data

49. Cho et al.

50. Spellman et al.

51. computational methods

52. Zhao et al.

53. Langmead et al.

54. Johansson et al.

55. Wichert et al.

56. Luan and Li

57. Lu et al.

58. Ahdesm äki et al.

59. Willbrand et al.

60. Chen

61. Qiu et al.

62. Ahnert et al.

63. Andersson et al.

64. Lu et al.

65. no benchmarking

66. reanalysis

67. benchmarking

69. no progress

70. no benchmarking

71. protein interactions

72. S. cerevisiae

73. Uetz et al.

74. Ito et al.

75. Gavin et al.

76. Ho et al.

77. topology-based scoring

78. quality threshold

79. subcellular localization

80. expression data

81. temporal network

83. benchmarking

86. 30–50% false positives

88. 3–5% false positives

89. detailed function prediction

90. uncharacterized proteins

91. who

92. whom

93. when

94. global statements

95. consistent timing

98. dynamic and static

101. just-in-time assembly

102. partial protein complexes

103. last missing subunits

104. post-translational regulation

105. phosphorylation

106. Übersax et al.

107. 27% of dynamic proteins

108. 8% of static proteins

109. targeted degradation

110. PEST regions

111. 44% of dynamic proteins

112. 29% of static proteins

113. undescribed link

114. transcriptional regulation

115. post-translational regulation

116. how can we test this?

117. cross-species comparison

118. evolutionary conservation

119. expression data

120. S. pombe

121. Rustici et al.

122. Peng et al.

123. Oliva et al.

124. no benchmarking

125. no integration

126. reanalysis

127. integration

128. benchmarking

130. no progress

131. no benchmarking

132. no integration

133. H. sapiens

134. Whitfield et al.

135. reanalysis

136. benchmarking

138. A. thaliana

139. Menges et al.

140. reanalysis

141. benchmarking

143. four organisms

144. list of genes

145. periodically expressed

146. orthology detection

147. sequence similarity

149. not conserved

150. individual genes

151. just-in-time assembly

152. protein complexes

157. different time scales

158. time warping

160. same color = same phase

161. just-in-time assembly

162. DNA polymerases

164. deoxynucleotide synthesis

166. phosphorylation

167. Übersax et al.

168. Loog et al.

169. Phospho.ELM

170. NetPhosK

171. correlation

174. cell cycle vs. non-cell cycle

175. co-evolution

178. transcriptional regulation

179. post-translational regulation

180. co-evolution

181. just-in-time assembly

182. multi-layer regulation

183. evolutionary flexibility

184. protein complexes

186. summary

187. reanalysis

188. integration

189. high-throughput data

190. reproduce what is know

191. biological discoveries

192. testable hypotheses

193. evolutionary conservation

195. Questions?