1. Lars Juhl Jensen
Systems biology
Bioinformatics on complete biological
systems

2. can a biologist fix a radio?

3. Lazebnik, Biochemistry, 2004

4. single gene studies

5. many experiments

6. knockout phenotype

7. Lazebnik, Biochemistry, 2004

8. everything about one gene

9. high-throughput biology

10. single technology

11. microarrays

13. one thing about every gene

14. systems biology

15. model complete systems

16. mathematical modeling

17. a simple system

18. Chen, Mol. Biol. Cell, 2004

19. simulation

20. Chen, Mol. Biol. Cell, 2004

21. many equations

22. Chen, Mol. Biol. Cell, 2004

23. many parameters

24. Chen, Mol. Biol. Cell, 2004

25. equires detailed knowledge

26. molecular networks

27. what is an interaction?

28. physical contact

29. stable interactions

30. transient interactions

31. interaction assays

32. yeast two-hybrid

33. fragment complementation

34. affinity purification

35. Jensen & Bork, Science, 2008

36. Jensen et al., Drug Discovery Today: TARGETS, 2004

37. spoke representation

38. Jensen et al., Drug Discovery Today: TARGETS, 2004

39. matrix representation

40. Jensen et al., Drug Discovery Today: TARGETS, 2004

41. interaction databases

42. BioGRID
General Repository for Interaction Datasets

43. DIP
Database of Interacting Proteins

44. IntAct

45. MINT
Molecular Interactions Database

46. Exercise 1
Go to http://thebiogrid.org
Query for human TYMS
Find the interaction partners
Check their sources
Think of possible problems

47. possibly many errors

48. purely high-throughput

49. one assay

50. one study

51. functional associations

52. guilt by association

54. STRING

55. experimental data

56. physical interactions

57. genetic interactions

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

59. gene coexpression

61. curated knowledge

62. complexes

63. pathways

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

65. genomic context

66. operons

67. Korbel et al., Nature Biotechnology, 2004

68. bidirectional promoters

69. Korbel et al., Nature Biotechnology, 2004

70. gene fusion

71. Korbel et al., Nature Biotechnology, 2004

72. phylogenetic profiles

73. Korbel et al., Nature Biotechnology, 2004

74. visualization

75. Franceschini et al., Nucleic Acids Research, 2013

76. many databases

77. different formats

78. different identifiers

79. variable quality

80. not comparable

81. not same species

82. hard work

83. (students)

84. quality scores

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

86. calibrate vs. gold standard

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

88. homology-based transfer

89. Franceschini et al., Nucleic Acids Research, 2013

90. Exercise 2
Query STRING for human TYMS
Show network in confidence mode
Show up to 20 interaction partners
Show only experimental evidence
Show also low-confidence links

91. text mining

92. >10 km

93. too much to read

94. computer

95. as smart as a dog

96. teach it specific tricks

99. named entity recognition

100. comprehensive lexicon

101. cyclin dependent kinase 1

102. CDC2

103. flexible matching

104. cyclin dependent kinase 1

105. cyclin-dependent kinase 1

106. orthographic variation

107. CDC2

108. hCdc2

109. “black list”

110. SDS

111. co-mentioning

112. within documents

113. within paragraphs

114. within sentences

115. scoring scheme

116. NLP
Natural Language Processing

117. grammatical analysis

118. Gene and protein names
Cue words for entity
recognition
Verbs for relation extraction
[nxexpr The expression of
[nxgene the cytochrome
genes
[nxpg CYC1 and CYC7]]]
is controlled by
[nxpg HAP1]

119. more precise

120. worse recall

121. related web resources

122. STITCH

123. STRING + 300k chemicals

125. drugs

126. metabolites

127. known drug targets

128. high-throughput screens

129. metabolic pathways

130. Exercise 3
Go to http://stitch-db.org
Query for human TYMS
What is the role of thymidylate?
What is the role of dUMP?
What is the role of Permetrexed?

131. general approach

132. suite of new resources

133. COMPARTMENTS

134. TISSUES

135. DISEASES

136. curated knowledge

137. experimental data

138. text mining

139. computational predictions

140. common identifiers

141. quality scores

142. visualization

143. compartments.jensenlab.org

144. tissues.jensenlab.org

145. thank you!