1. STRING Modeling of biological systems through cross-species data integration

2. Lars Juhl Jensen

5. promoter analysis

6. Jensen et al., Bioinformatics, 2000

7. genome visualization

8. Pedersen et al., Journal of Molecular Biology, 2000

9. protein function prediction

13. STRING

15. integrate diverse evidence

16. functional interactions

17. Bork et al., Current Opinion in Structural Biology, 2005

18. 179 proteomes

19. genomic context methods

20. phylogenetic profiles

25. Cell Cellulosomes Cellulose

26. anti-correlated profiles

28. analogous enzymes

29. Morett et al., Nature Biotechnology, 2003

30. gene neighborhood

32. bidirectional promoters

34. Korbel et al., Nature Biotechnology, 2004

35. gene fusion

37. evolution

40. statistics

41. (the original sin)

42. scoring and benchmarking

43. raw quality scores

44. gene neighborhood

45. sum of intergenic distances

47. many types of evidence

48. not directly comparable

49. calibrate vs. gold standard

51. curated knowledge

52. KEGG Kyoto Encyclopedia of Genes and Genomes

53. STKE Signal Transduction Knowledge Environment

54. Reactome

55. MIPS Munich Information center for Protein Sequences

56. primary experimental data

57. Jensen et al., Drug Discovery Today: Targets, 2004

58. microarray expression data

59. GEO Gene Expression Omnibus

60. physical protein interactions

61. BIND Biomolecular Interaction Network Database

62. MINT Molecular Interactions Database

63. GRID General Repository for Interaction Datasets

64. DIP Database of Interacting Proteins

65. HPRD Human Protein Reference Database

66. von Mering et al., Nucleic Acids Research, 2005

67. literature mining

68. M EDLINE

69. SGD Saccharomyces Genome Database

70. The Interactive Fly

71. OMIM Online Mendelian Inheritance in Man

72. co-mentioning

73. different gene names

74. curated synonyms lists

75. NLP Natural Language Processing

76. Gene and protein names Cue words for entity recognition Verbs for relation extraction [ nxgene The GAL4 gene] [ nxexpr The expression of [ nxgene the cytochrome genes [ nxpg CYC1 and CYC7]]] is controlled by [ nxpg HAP1]

77. Jensen et al., Nature Reviews Genetics, 2006

78. combine all evidence

79. naïve Bayesian scheme

80. spread over many species

81. transfer based orthology

82. ? Source species Target species

89. defining functional modules

92. qualitative modeling

93. the mitochondrial system

95. RCCs

96. predicting “mode of action”

97. Jensen et al., Drug Discovery Today: Targets, 2004

99. Acknowledgments The STRING team (EMBL) –Christian von Mering –Berend Snel –Martijn Huynen –Sean Hooper –Mathilde Foglierini –Julien Lagarde –Peer Bork Literature mining project (EML Research) –Jasmin Saric –Rossitza Ouzounova –Isabel Rojas New genomic context methods (EMBL) –Jan Korbel –Peer Bork Modeling of yeast mitochondria (EMBL) –Fabiana Perocchi –Lars Steinmetz Inspiration for presentation –Dick Clarence Hardt –Anders Gorm Pedersen

100. Thank you!