Using networks to derive function Lars Juhl Jensen
STRING
Jensen, Kuhn et al.,  Nucleic Acids Research , 2009
functional associations
Frishman et al.,  Modern Genome Annotation , 2009
common basis
630 genomes
model organism databases
Ensembl
RefSeq
genomic context methods
gene fusion
Korbel et al.,  Nature Biotechnology , 2004
conserved neighborhood
operons
Korbel et al.,  Nature Biotechnology , 2004
bidirectional promoters
Korbel et al.,  Nature Biotechnology , 2004
phylogenetic profiles
Korbel et al.,  Nature Biotechnology , 2004
primary experimental data
protein interactions
yeast two-hybrid
affinity purification
fragment complementation
Jensen & Bork,  Science , 2008
genetic interactions
Beyer et al.,  Nature Reviews Genetics , 2007
BIND Biomolecular Interaction Network Database
BioGRID General Repository for Interaction Datasets
DIP Database of Interacting Proteins
IntAct
MINT Molecular Interactions Database
HPRD Human Protein Reference Database
PDB Protein Data Bank
inferred associations
gene coexpression
 
GEO Gene Expression Omnibus
expression compendia
curated knowledge
complexes
MIPS Munich Information center for Protein Sequences
Gene Ontology
pathways
Letunic & Bork,  Trends in Biochemical Sciences , 2008
KEGG Kyoto Encyclopedia of Genes and Genomes
MetaCyc
Reactome
PID NCI-Nature Pathway Interaction Database
literature mining
M EDLINE
SGD Saccharomyces Genome Database
The Interactive Fly
OMIM Online Mendelian Inheritance in Man
co-mentioning
statistical methods
NLP Natural Language Processing
<ul><li>Gene  and protein  names </li></ul><ul><li>Cue words for entity recognition </li></ul><ul><li>Verbs for relation e...
 
easy in theory …
…  but not in practice
many data types
not comparable
variable quality
many sources
different file formats
different gene identifiers
partially redundant
spread over 630 genomes
quality scores
reproducibility
von Mering et al.,  Nucleic Acids Research , 2005
benchmarking
von Mering et al.,  Nucleic Acids Research , 2005
orthology
von Mering et al.,  Nucleic Acids Research , 2005
two modes
COG mode
von Mering et al.,  Nucleic Acids Research , 2005
protein mode
von Mering et al.,  Nucleic Acids Research , 2005
combine all evidence
Frishman et al.,  Modern Genome Annotation , 2009
Acknowledgments <ul><li>Christian von Mering </li></ul><ul><li>Michael Kuhn </li></ul><ul><li>Manuel Stark </li></ul><ul><...
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Using networks to derive function

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Systems Biology Workshop, Technical University of Denmark, Lyngy, Denmark, May 14-15, 2009

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Using networks to derive function

  1. 1. Using networks to derive function Lars Juhl Jensen
  2. 2. STRING
  3. 3. Jensen, Kuhn et al., Nucleic Acids Research , 2009
  4. 4. functional associations
  5. 5. Frishman et al., Modern Genome Annotation , 2009
  6. 6. common basis
  7. 7. 630 genomes
  8. 8. model organism databases
  9. 9. Ensembl
  10. 10. RefSeq
  11. 11. genomic context methods
  12. 12. gene fusion
  13. 13. Korbel et al., Nature Biotechnology , 2004
  14. 14. conserved neighborhood
  15. 15. operons
  16. 16. Korbel et al., Nature Biotechnology , 2004
  17. 17. bidirectional promoters
  18. 18. Korbel et al., Nature Biotechnology , 2004
  19. 19. phylogenetic profiles
  20. 20. Korbel et al., Nature Biotechnology , 2004
  21. 21. primary experimental data
  22. 22. protein interactions
  23. 23. yeast two-hybrid
  24. 24. affinity purification
  25. 25. fragment complementation
  26. 26. Jensen & Bork, Science , 2008
  27. 27. genetic interactions
  28. 28. Beyer et al., Nature Reviews Genetics , 2007
  29. 29. BIND Biomolecular Interaction Network Database
  30. 30. BioGRID General Repository for Interaction Datasets
  31. 31. DIP Database of Interacting Proteins
  32. 32. IntAct
  33. 33. MINT Molecular Interactions Database
  34. 34. HPRD Human Protein Reference Database
  35. 35. PDB Protein Data Bank
  36. 36. inferred associations
  37. 37. gene coexpression
  38. 39. GEO Gene Expression Omnibus
  39. 40. expression compendia
  40. 41. curated knowledge
  41. 42. complexes
  42. 43. MIPS Munich Information center for Protein Sequences
  43. 44. Gene Ontology
  44. 45. pathways
  45. 46. Letunic & Bork, Trends in Biochemical Sciences , 2008
  46. 47. KEGG Kyoto Encyclopedia of Genes and Genomes
  47. 48. MetaCyc
  48. 49. Reactome
  49. 50. PID NCI-Nature Pathway Interaction Database
  50. 51. literature mining
  51. 52. M EDLINE
  52. 53. SGD Saccharomyces Genome Database
  53. 54. The Interactive Fly
  54. 55. OMIM Online Mendelian Inheritance in Man
  55. 56. co-mentioning
  56. 57. statistical methods
  57. 58. NLP Natural Language Processing
  58. 59. <ul><li>Gene and protein names </li></ul><ul><li>Cue words for entity recognition </li></ul><ul><li>Verbs for relation extraction </li></ul><ul><li>[ nxgene The GAL4 gene ] </li></ul><ul><li>[ nxexpr T he expression of [ nxgene the cytochrome genes [ nxpg CYC1 and CYC7 ]]] is controlled by [ nxpg HAP1 ] </li></ul>
  59. 61. easy in theory …
  60. 62. … but not in practice
  61. 63. many data types
  62. 64. not comparable
  63. 65. variable quality
  64. 66. many sources
  65. 67. different file formats
  66. 68. different gene identifiers
  67. 69. partially redundant
  68. 70. spread over 630 genomes
  69. 71. quality scores
  70. 72. reproducibility
  71. 73. von Mering et al., Nucleic Acids Research , 2005
  72. 74. benchmarking
  73. 75. von Mering et al., Nucleic Acids Research , 2005
  74. 76. orthology
  75. 77. von Mering et al., Nucleic Acids Research , 2005
  76. 78. two modes
  77. 79. COG mode
  78. 80. von Mering et al., Nucleic Acids Research , 2005
  79. 81. protein mode
  80. 82. von Mering et al., Nucleic Acids Research , 2005
  81. 83. combine all evidence
  82. 84. Frishman et al., Modern Genome Annotation , 2009
  83. 85. Acknowledgments <ul><li>Christian von Mering </li></ul><ul><li>Michael Kuhn </li></ul><ul><li>Manuel Stark </li></ul><ul><li>Samuel Chaffron </li></ul><ul><li>Philippe Julien </li></ul><ul><li>Tobias Doerks </li></ul><ul><li>Jan Korbel </li></ul><ul><li>Berend Snel </li></ul><ul><li>Martijn Huynen </li></ul><ul><li>Peer Bork </li></ul>

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