Systems biology: Bioinformatics on complete biological system
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Systems biology: Bioinformatics on complete biological system Presentation Transcript

  • 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
  • 12. one thing about every gene
  • 13. systems biology
  • 14. model complete systems
  • 15. mathematical modeling
  • 16. a simple system
  • 17. Chen, Mol. Biol. Cell, 2004
  • 18. simulation
  • 19. Chen, Mol. Biol. Cell, 2004
  • 20. many equations
  • 21. Chen, Mol. Biol. Cell, 2004
  • 22. many parameters
  • 23. Chen, Mol. Biol. Cell, 2004
  • 24. equires detailed knowledge
  • 25. molecular networks
  • 26. what is an interaction?
  • 27. physical contact
  • 28. stable interactions
  • 29. transient interactions
  • 30. interaction assays
  • 31. yeast two-hybrid
  • 32. fragment complementation
  • 33. affinity purification
  • 34. Jensen & Bork, Science, 2008
  • 35. Jensen et al., Drug Discovery Today: TARGETS, 2004
  • 36. spoke representation
  • 37. Jensen et al., Drug Discovery Today: TARGETS, 2004
  • 38. matrix representation
  • 39. Jensen et al., Drug Discovery Today: TARGETS, 2004
  • 40. interaction databases
  • 41. BioGRID General Repository for Interaction Datasets
  • 42. DIP Database of Interacting Proteins
  • 43. IntAct
  • 44. MINT Molecular Interactions Database
  • 45. Exercise 1 Go to http://thebiogrid.org Query for human TYMS Find the interaction partners Check their sources Think of possible problems
  • 46. possibly many errors
  • 47. purely high-throughput
  • 48. one assay
  • 49. one study
  • 50. functional associations
  • 51. guilt by association
  • 52. STRING
  • 53. experimental data
  • 54. physical interactions
  • 55. genetic interactions
  • 56. Beyer et al., Nature Reviews Genetics, 2007
  • 57. gene coexpression
  • 58. curated knowledge
  • 59. complexes
  • 60. pathways
  • 61. Letunic & Bork, Trends in Biochemical Sciences, 2008
  • 62. genomic context
  • 63. operons
  • 64. Korbel et al., Nature Biotechnology, 2004
  • 65. bidirectional promoters
  • 66. Korbel et al., Nature Biotechnology, 2004
  • 67. gene fusion
  • 68. Korbel et al., Nature Biotechnology, 2004
  • 69. phylogenetic profiles
  • 70. Korbel et al., Nature Biotechnology, 2004
  • 71. visualization
  • 72. Franceschini et al., Nucleic Acids Research, 2013
  • 73. many databases
  • 74. different formats
  • 75. different identifiers
  • 76. variable quality
  • 77. not comparable
  • 78. not same species
  • 79. hard work
  • 80. (students)
  • 81. quality scores
  • 82. von Mering et al., Nucleic Acids Research, 2005
  • 83. calibrate vs. gold standard
  • 84. von Mering et al., Nucleic Acids Research, 2005
  • 85. homology-based transfer
  • 86. Franceschini et al., Nucleic Acids Research, 2013
  • 87. 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
  • 88. text mining
  • 89. >10 km
  • 90. too much to read
  • 91. computer
  • 92. as smart as a dog
  • 93. teach it specific tricks
  • 94. named entity recognition
  • 95. comprehensive lexicon
  • 96. cyclin dependent kinase 1
  • 97. CDC2
  • 98. flexible matching
  • 99. cyclin dependent kinase 1
  • 100. cyclin-dependent kinase 1
  • 101. orthographic variation
  • 102. CDC2
  • 103. hCdc2
  • 104. “black list”
  • 105. SDS
  • 106. co-mentioning
  • 107. within documents
  • 108. within paragraphs
  • 109. within sentences
  • 110. scoring scheme
  • 111. NLP Natural Language Processing
  • 112. grammatical analysis
  • 113. 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]
  • 114. more precise
  • 115. worse recall
  • 116. related web resources
  • 117. STITCH
  • 118. STRING + 300k chemicals
  • 119. drugs
  • 120. metabolites
  • 121. known drug targets
  • 122. high-throughput screens
  • 123. metabolic pathways
  • 124. 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?
  • 125. general approach
  • 126. suite of new resources
  • 127. COMPARTMENTS
  • 128. TISSUES
  • 129. DISEASES
  • 130. curated knowledge
  • 131. experimental data
  • 132. text mining
  • 133. computational predictions
  • 134. common identifiers
  • 135. quality scores
  • 136. visualization
  • 137. compartments.jensenlab.org
  • 138. tissues.jensenlab.org
  • 139. thank you!