Systems biology
Large-scale biomedical data mining
Lars Juhl Jensen
Phase 1
association networks
who?
protein networks
Jensen, Kuhn et al., Nucleic Acids Research, 2009
genomic context
gene fusion
Korbel et al., Nature Biotechnology, 2004
conserved neighborhood
Korbel et al., Nature Biotechnology, 2004
phylogenetic profiles
Korbel et al., Nature Biotechnology, 2004
gene coexpression
protein interactions
Jensen & Bork, Science, 2008
genetic interactions
Beyer et al., Nature Reviews Genetics, 2007
curated knowledge
Letunic & Bork, Trends in Biochemical Sciences, 2008
>10 km
text mining
Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
co-mentioning
NLP
Natural Language Processing
different formats
different names
variable quality
not comparable
spread over 630 genomes
confidence scores
von Mering et al., Nucleic Acids Research, 2005
transfer by orthology
von Mering et al., Nucleic Acids Research, 2005
Frishman et al., Modern Genome Annotation, 2009
Phase 2
signaling networks
what?
phosphoproteomics
kinases are unknown
sequence motifs
machine-learning methods
Miller, Jensen et al., Science Signaling, 2008
peptide assays
Miller, Jensen et al., Science Signaling, 2008
automated pipeline
Miller, Jensen et al., Science Signaling, 2008
sequence specificity
no context
network context
Linding, Jensen, Ostheimer et al., Cell, 2007
Linding, Jensen, Ostheimer et al., Cell, 2007
>2x better accuracy
context is crucial
example
DNA damage response
Linding, Jensen, Ostheimer et al., Cell, 2007
small-scale validation
Linding, Jensen, Ostheimer et al., Cell, 2007
Phase 3
dynamic networks
when?
cell-cycle regulation
microarray time courses
Gauthier et al., Nucleic Acids Research, 2007
protein interactions
temporal network
de Lichtenberg, Jensen et al., Science, 2005
de Lichtenberg, Jensen et al., Science, 2005
just-in-time assembly
de Lichtenberg, Jensen et al., Cell Cycle, 2007
evolutionary flexibility
individual genes
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
protein complexes
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
phosphorylation
co-evolution
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
summary
data mining
specific predictions
systems properties
thank you!
Acknowledgments
NetPhorest.info
– Rune Linding
– Martin Lee Miller
– Francesca Diella
– Claus Jørgensen
– Michele Tinti
– ...
larsjuhljensen
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
Systems biology: Large-scale biomedical data mining
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  • Integration
    Automation
    Collaboration
  • Atlas of human kinases
    Atlases for phospho-binding proteins
    Atlases for model organisms
    Ubiquitination would be welcome
  • Systems biology: Large-scale biomedical data mining

    1. 1. Systems biology Large-scale biomedical data mining Lars Juhl Jensen
    2. 2. Phase 1 association networks
    3. 3. who?
    4. 4. protein networks
    5. 5. Jensen, Kuhn et al., Nucleic Acids Research, 2009
    6. 6. genomic context
    7. 7. gene fusion
    8. 8. Korbel et al., Nature Biotechnology, 2004
    9. 9. conserved neighborhood
    10. 10. Korbel et al., Nature Biotechnology, 2004
    11. 11. phylogenetic profiles
    12. 12. Korbel et al., Nature Biotechnology, 2004
    13. 13. gene coexpression
    14. 14. protein interactions
    15. 15. Jensen & Bork, Science, 2008
    16. 16. genetic interactions
    17. 17. Beyer et al., Nature Reviews Genetics, 2007
    18. 18. curated knowledge
    19. 19. Letunic & Bork, Trends in Biochemical Sciences, 2008
    20. 20. >10 km
    21. 21. text mining
    22. 22. Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
    23. 23. co-mentioning
    24. 24. NLP Natural Language Processing
    25. 25. different formats
    26. 26. different names
    27. 27. variable quality
    28. 28. not comparable
    29. 29. spread over 630 genomes
    30. 30. confidence scores
    31. 31. von Mering et al., Nucleic Acids Research, 2005
    32. 32. transfer by orthology
    33. 33. von Mering et al., Nucleic Acids Research, 2005
    34. 34. Frishman et al., Modern Genome Annotation, 2009
    35. 35. Phase 2 signaling networks
    36. 36. what?
    37. 37. phosphoproteomics
    38. 38. kinases are unknown
    39. 39. sequence motifs
    40. 40. machine-learning methods
    41. 41. Miller, Jensen et al., Science Signaling, 2008
    42. 42. peptide assays
    43. 43. Miller, Jensen et al., Science Signaling, 2008
    44. 44. automated pipeline
    45. 45. Miller, Jensen et al., Science Signaling, 2008
    46. 46. sequence specificity
    47. 47. no context
    48. 48. network context
    49. 49. Linding, Jensen, Ostheimer et al., Cell, 2007
    50. 50. Linding, Jensen, Ostheimer et al., Cell, 2007
    51. 51. >2x better accuracy
    52. 52. context is crucial
    53. 53. example
    54. 54. DNA damage response
    55. 55. Linding, Jensen, Ostheimer et al., Cell, 2007
    56. 56. small-scale validation
    57. 57. Linding, Jensen, Ostheimer et al., Cell, 2007
    58. 58. Phase 3 dynamic networks
    59. 59. when?
    60. 60. cell-cycle regulation
    61. 61. microarray time courses
    62. 62. Gauthier et al., Nucleic Acids Research, 2007
    63. 63. protein interactions
    64. 64. temporal network
    65. 65. de Lichtenberg, Jensen et al., Science, 2005
    66. 66. de Lichtenberg, Jensen et al., Science, 2005
    67. 67. just-in-time assembly
    68. 68. de Lichtenberg, Jensen et al., Cell Cycle, 2007
    69. 69. evolutionary flexibility
    70. 70. individual genes
    71. 71. Jensen, Jensen, de Lichtenberg et al., Nature, 2006
    72. 72. protein complexes
    73. 73. Jensen, Jensen, de Lichtenberg et al., Nature, 2006
    74. 74. phosphorylation
    75. 75. co-evolution
    76. 76. Jensen, Jensen, de Lichtenberg et al., Nature, 2006
    77. 77. summary
    78. 78. data mining
    79. 79. specific predictions
    80. 80. systems properties
    81. 81. thank you!
    82. 82. Acknowledgments NetPhorest.info – Rune Linding – Martin Lee Miller – Francesca Diella – Claus Jørgensen – Michele Tinti – Lei Li – Marilyn Hsiung – Sirlester A. Parker – Jennifer Bordeaux – Thomas Sicheritz-Pontén – Marina Olhovsky – Adrian Pasculescu – Jes Alexander – Stefan Knapp – Nikolaj Blom – Peer Bork – Shawn Li – Gianni Cesareni – Tony Pawson – Benjamin E. Turk – Michael B. Yaffe – Søren Brunak STRING-DB.org – Christian von Mering – Damian Szklarczyk – Michael Kuhn – Manuel Stark – Samuel Chaffron – Chris Creevey – Jean Muller – Tobias Doerks – Philippe Julien – Alexander Roth – Milan Simonovic – Jan Korbel – Berend Snel – Martijn Huynen – Peer Bork Reflect.ws – Sune Frankild – Heiko Horn – Evangelos Pafilis – Michael Kuhn – Nigel Brown – Reinhardt Schneider – Sean O’Donoghue NetworKIN.info – Rune Linding – Heiko Horn – Gerard Ostheimer – Martin Lee Miller – Francesca Diella – Karen Colwill – Jing Jin – Pavel Metalnikov – Vivian Nguyen – Adrian Pasculescu – Jin Gyoon Park – Leona D. Samson – Rob Russell – Peer Bork – Michael Yaffe – Tony Pawson Cyclebase.org – Ulrik de Lichtenberg – Thomas Skøt Jensen – Nicholas Paul Gauthier – Rasmus Wernersson – Søren Brunak
    83. 83. larsjuhljensen

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