Protein interactions

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Lars Juhl Jensen

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

BioGRID
General Repository for Interaction Datasets

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

Franceschini et al., Nucleic Acids Research, 2013

Exercise 2
Go to http://string-db.org
Query for human TYMS
Show only highest confidence
Show network in confidence view
Show network in evidence view

Korbel et al., Nature Biotechnology, 2004

Beyer et al., Nature Reviews Genetics, 2007

Letunic & Bork, Trends in Biochemical Sciences, 2008

von Mering et al., Nucleic Acids Research, 2005

Exercise 3
Query STRING for human TYMS
Show only experimental evidence
Show up to 50 interaction partners
Show also low-confidence links
Redo exercise for mouse TYMS

Exercise 4
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?

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Protein interactions

1. Protein interactions Lars Juhl Jensen

2. what is an interaction?

3. physical interaction

4. functional association

5. fuzzy definitions

6. physical interactions

7. stable interactions

8. transient interactions

9. binary interactions

10. multimeric complexes

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

12. spoke representation

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

14. matrix representation

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

16. interaction assays

17. yeast two-hybrid

18. fragment complementation

19. affinity purification

20. Jensen & Bork, Science, 2008

21. interaction databases

22. BioGRID General Repository for Interaction Datasets

23. DIP Database of Interacting Proteins

24. IntAct

25. MINT Molecular Interactions Database

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

27. possibly many errors

28. only high-throughput

29. one assay

30. one study

31. functional associations

32. guilt by association

33.

34. STRING

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

36. Exercise 2 Go to http://string-db.org Query for human TYMS Show only highest confidence Show network in confidence view Show network in evidence view

37. genomic context

38. operons

39. Korbel et al., Nature Biotechnology, 2004

40. bidirectional promoters

41. Korbel et al., Nature Biotechnology, 2004

42. gene fusion

43. Korbel et al., Nature Biotechnology, 2004

44. phylogenetic profiles

45. Korbel et al., Nature Biotechnology, 2004

46. a real example

47.

48.

49.

50. Cell Cellulosomes Cellulose

51. experimental data

52. physical interactions

53. Jensen & Bork, Science, 2008

54. genetic interactions

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

56. gene coexpression

57.

58. text mining

59. co-mentioning

60.

61. curated knowledge

62. complexes

63. pathways

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

65. many databases

66. different formats

67. different identifiers

68. variable quality

69. not comparable

70. not same species

71. hard work

72. (graduate students)

73. quality scores

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

75. calibrate vs. gold standard

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

77. homology-based transfer

78. orthologs vs. paralogs

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

80. Exercise 3 Query STRING for human TYMS Show only experimental evidence Show up to 50 interaction partners Show also low-confidence links Redo exercise for mouse TYMS

81. related web resources

82. STITCH

83. STRING + 300k chemicals

84.

85. drugs

86. metabolites

87. known drug targets

88. high-throughput screens

89. metabolic pathways

90. Exercise 4 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?

91. general approach

92. suite of new resources

93. COMPARTMENTS

94. TISSUES

95. DISEASES

96. curated knowledge

97. experimental data

98. text mining

99. computational predictions

100. common identifiers

101. quality scores

102. visualization