1. Systems biology
Understanding biology at the systems level
Lars Juhl Jensen

2. traditional biology

3. can a biologist fix a radio?

4. Lazebnik, Biochemistry, 2004

5. one gene

6. one postdoc

7. all aspects

8. knockout phenotype

9. Lazebnik, Biochemistry, 2004

10. one gene

11. high-throughput biology

12. one technology

13. one lab

14. all genes

15. one aspect

16. systems biology

17. complete systems

18. all aspects

19. all genes

20. systems-level properties

21. two subfields

22. mathematical modeling

23. small systems

24. data integration

25. large systems

26. the system

27. mitotic cell cycle

28. grow and divide

29. one cell

30. two cells

31. four phases

32. G1 phase

33. growth

34. S phase

35. DNA replication

36. G2 phase

37. growth

38. M phase

39. cell division

41. regulation

42. gene expression

43. phosphorylation

44. targeted degradation

45. protein interactions

46. cell cycle modeling

47. core cell cycle

48. Chen, Mol. Biol. Cell, 2004

49. many equations

50. Chen, Mol. Biol. Cell, 2004

51. simulation

52. Chen, Mol. Biol. Cell, 2004

53. many parameters

54. Chen, Mol. Biol. Cell, 2004

55. requires detailed knowledge

56. cell cycle analysis

57. gene expression

58. cell cultures

59. synchronization

60. microarrays

62. time courses

63. Gauthier et al., Nucleic Acids Research, 2007

64. cycling genes

65. time of peak expression

66. exercise 1

67. http://cyclebase.org

68. S. cerevisiae

69. RNR1, RNR2, RNR3, RNR4

70. S. pombe

71. cdc22, suc22

72. which genes cycle?

73. do time courses agree?

74. do orthologs agree?

75. do paralogs agree?

76. protein networks

77. guilt by association

79. STRING

80. >1100 genomes

81. genomic context

82. gene fusion

83. Korbel et al., Nature Biotechnology, 2004

84. conserved neighborhood

85. Korbel et al., Nature Biotechnology, 2004

86. phylogenetic profiles

87. Korbel et al., Nature Biotechnology, 2004

88. protein interactions

89. Jensen & Bork, Science, 2008

90. genetic interactions

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

92. gene coexpression

94. curated knowledge

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

96. >10 km

97. text mining

98. Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009

99. co-mentioning

100. NLP
Natural Language Processing

101. different sources

102. Ensembl

103. RefSeq

104. BIND
Biomolecular Interaction Network Database

105. BioGRID
General Repository for Interaction Datasets

106. DIP
Database of Interacting Proteins

107. IntAct

108. MINT
Molecular Interactions Database

109. HPRD
Human Protein Reference Database

110. PDB
Protein Data Bank

111. GEO
Gene Expression Omnibus

112. MIPS
Munich Information center
for Protein Sequences

113. Gene Ontology

114. BioCyc

115. KEGG
Kyoto Encyclopedia of Genes and Genomes

116. PID
NCI-Nature Pathway Interaction Database

117. Reactome

118. different formats

119. different names

120. CDC2

121. CDK1

122. P06493

123. not comparable

124. variable quality

125. confidence scores

126. calibrate to gold standard

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

128. transfer by orthology

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

130. combine scores

131. exercise 2

132. http://string-db.org

133. Szklarczyk, Franceschini et al., Nucleic Acids Research, 2011

136. changing parameters

138. high confidence only

140. experiments only

142. evidence viewers

144. which interact functionally?

145. which interact physically?

146. complex regulation

147. time of peak expression

149. protein interactions

150. temporal network

151. de Lichtenberg, Jensen et al., Science, 2005

152. dynamic vs. static subunits

153. de Lichtenberg, Jensen et al., Science, 2005

154. just-in-time assembly

155. de Lichtenberg, Jensen et al., Cell Cycle, 2007

156. evolutionary flexibility

157. orthologs and paralogs

158. Jensen, Jensen, de Lichtenberg et al., Nature, 2006

159. protein complexes

160. Jensen, Jensen, de Lichtenberg et al., Nature, 2006

161. exercise 3

162. http://cyclebase-string.jensenlab.org

165. network expansion

168. what does SML1 do?

169. when is SML1 expressed?

170. how does that make sense?

171. multi-layer regulation

172. phosphorylation

174. CDK substrates

175. low-throughput data

176. high-throughput data

177. NetPhosK

178. correlation

179. Jensen, Jensen, de Lichtenberg et al., Nature, 2006

180. Jensen, Jensen, de Lichtenberg et al., Nature, 2006

181. bias

182. correlated changes

183. removes the bias

184. Jensen, Jensen, de Lichtenberg et al., Nature, 2006

185. co-evolution

186. disease networks

187. human proteins

188. >8,000 disease terms

189. text mining

190. co-mentioning

191. exercise 4

192. http://diseases.jensenlab.org

193. TYMS disease associations

196. inspect the evidence

198. colorectal cancer network

201. chemical networks

202. STITCH

203. STRING + chemicals

204. PubChem compounds

205. >74,000 small molecules

206. experimental data

207. BindingDB

208. ChEMBL

209. PDSP Ki
Psycoactive Drug Screening Program

210. PDB
Protein Data Bank

211. drug targets

212. CTD
Comparative Toxicogenomics Database

213. DrugBank

214. GLIDA
GPCR-Ligand Database

215. Matador

216. TTD
Therapeutic Target Database

217. metabolic pathways

218. BioCyc

219. KEGG
Kyoto Encyclopedia of Genes and Genomes

220. Reactome

221. text mining

222. co-mentioning

223. NLP
Natural Language Processing

224. same issues as for proteins

225. only worse

226. exercise 5

227. http://stitch-db.org

228. chemical network for TYMS

229. Kuhn et al., Nucleic Acids Research, 2012

231. network expansion

233. which role has thymidylate?

234. which role has dUMP?

235. which role has Pemetrexed?