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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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