Protein interactions

Lars Juhl Jensen
what is an interaction?
physical interaction
functional association
fuzzy definitions
physical interactions
stable interactions
transient interactions
binary interactions
multimeric complexes
Jensen et al., Drug Discovery Today: TARGETS, 2004
spoke representation
Jensen et al., Drug Discovery Today: TARGETS, 2004
matrix representation
Jensen et al., Drug Discovery Today: TARGETS, 2004
interaction assays
yeast two-hybrid
fragment complementation
affinity purification
Jensen & Bork, Science, 2008
interaction databases
BioGRID
General Repository for Interaction Datasets
DIP
Database of Interacting Proteins
IntAct
MINT
Molecular Interactions Database
Exercise 1
Go to http://thebiogrid.org
Query for human TYMS
Find the interaction partners
Check their sources
Think of pos...
possibly many errors
only high-throughput
one assay
one study
functional associations
guilt by association
STRING
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
Sh...
genomic context
operons
Korbel et al., Nature Biotechnology, 2004
bidirectional promoters
Korbel et al., Nature Biotechnology, 2004
gene fusion
Korbel et al., Nature Biotechnology, 2004
phylogenetic profiles
Korbel et al., Nature Biotechnology, 2004
a real example
Cell

Cellulosomes

Cellulose
experimental data
physical interactions
Jensen & Bork, Science, 2008
genetic interactions
Beyer et al., Nature Reviews Genetics, 2007
gene coexpression
text mining
co-mentioning
curated knowledge
complexes
pathways
Letunic & Bork, Trends in Biochemical Sciences, 2008
many databases
different formats
different identifiers
variable quality
not comparable
not same species
hard work
(graduate students)
quality scores
von Mering et al., Nucleic Acids Research, 2005
calibrate vs. gold standard
von Mering et al., Nucleic Acids Research, 2005
homology-based transfer
orthologs vs. paralogs
Franceschini et al., Nucleic Acids Research, 2013
Exercise 3
Query STRING for human TYMS
Show only experimental evidence
Show up to 50 interaction partners
Show also low-co...
related web resources
STITCH
STRING + 300k chemicals
drugs
metabolites
known drug targets
high-throughput screens
metabolic pathways
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...
general approach
suite of new resources
COMPARTMENTS
TISSUES
DISEASES
curated knowledge
experimental data
text mining
computational predictions
common identifiers
quality scores
visualization
compartments.jensenlab.org
tissues.jensenlab.org
thank you!
Protein interactions
Protein interactions
Protein interactions
Protein interactions
Protein interactions
Protein interactions
Protein interactions
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  • Protein interactions

    1. 1. Protein interactions Lars Juhl Jensen
    2. 2. what is an interaction?
    3. 3. physical interaction
    4. 4. functional association
    5. 5. fuzzy definitions
    6. 6. physical interactions
    7. 7. stable interactions
    8. 8. transient interactions
    9. 9. binary interactions
    10. 10. multimeric complexes
    11. 11. Jensen et al., Drug Discovery Today: TARGETS, 2004
    12. 12. spoke representation
    13. 13. Jensen et al., Drug Discovery Today: TARGETS, 2004
    14. 14. matrix representation
    15. 15. Jensen et al., Drug Discovery Today: TARGETS, 2004
    16. 16. interaction assays
    17. 17. yeast two-hybrid
    18. 18. fragment complementation
    19. 19. affinity purification
    20. 20. Jensen & Bork, Science, 2008
    21. 21. interaction databases
    22. 22. BioGRID General Repository for Interaction Datasets
    23. 23. DIP Database of Interacting Proteins
    24. 24. IntAct
    25. 25. MINT Molecular Interactions Database
    26. 26. Exercise 1 Go to http://thebiogrid.org Query for human TYMS Find the interaction partners Check their sources Think of possible problems
    27. 27. possibly many errors
    28. 28. only high-throughput
    29. 29. one assay
    30. 30. one study
    31. 31. functional associations
    32. 32. guilt by association
    33. 33. STRING
    34. 34. Franceschini et al., Nucleic Acids Research, 2013
    35. 35. 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
    36. 36. genomic context
    37. 37. operons
    38. 38. Korbel et al., Nature Biotechnology, 2004
    39. 39. bidirectional promoters
    40. 40. Korbel et al., Nature Biotechnology, 2004
    41. 41. gene fusion
    42. 42. Korbel et al., Nature Biotechnology, 2004
    43. 43. phylogenetic profiles
    44. 44. Korbel et al., Nature Biotechnology, 2004
    45. 45. a real example
    46. 46. Cell Cellulosomes Cellulose
    47. 47. experimental data
    48. 48. physical interactions
    49. 49. Jensen & Bork, Science, 2008
    50. 50. genetic interactions
    51. 51. Beyer et al., Nature Reviews Genetics, 2007
    52. 52. gene coexpression
    53. 53. text mining
    54. 54. co-mentioning
    55. 55. curated knowledge
    56. 56. complexes
    57. 57. pathways
    58. 58. Letunic & Bork, Trends in Biochemical Sciences, 2008
    59. 59. many databases
    60. 60. different formats
    61. 61. different identifiers
    62. 62. variable quality
    63. 63. not comparable
    64. 64. not same species
    65. 65. hard work
    66. 66. (graduate students)
    67. 67. quality scores
    68. 68. von Mering et al., Nucleic Acids Research, 2005
    69. 69. calibrate vs. gold standard
    70. 70. von Mering et al., Nucleic Acids Research, 2005
    71. 71. homology-based transfer
    72. 72. orthologs vs. paralogs
    73. 73. Franceschini et al., Nucleic Acids Research, 2013
    74. 74. 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
    75. 75. related web resources
    76. 76. STITCH
    77. 77. STRING + 300k chemicals
    78. 78. drugs
    79. 79. metabolites
    80. 80. known drug targets
    81. 81. high-throughput screens
    82. 82. metabolic pathways
    83. 83. 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?
    84. 84. general approach
    85. 85. suite of new resources
    86. 86. COMPARTMENTS
    87. 87. TISSUES
    88. 88. DISEASES
    89. 89. curated knowledge
    90. 90. experimental data
    91. 91. text mining
    92. 92. computational predictions
    93. 93. common identifiers
    94. 94. quality scores
    95. 95. visualization
    96. 96. compartments.jensenlab.org
    97. 97. tissues.jensenlab.org
    98. 98. thank you!

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