Data integration - Integration of functional associations using STRING

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Lars Juhl Jensen

EMBO World Practical Course on Computational Biology, Shanghai Jiao Tong University, Shanghai, China, August 22, 2009.

Data integration Integration of functional associations using STRING Lars Juhl Jensen

Jensen, Kuhn et al., Nucleic Acids Research , 2009

functional associations

confidence scores

cross-species integration

630 genomes

model organism databases

Ensembl

RefSeq

defining orthology

two modes

protein mode

von Mering et al., Nucleic Acids Research , 2005

COG mode

von Mering et al., Nucleic Acids Research , 2005

genomic context

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

examples

bacterial Cox assembly

Banci et al., PNAS , 2005

Banci et al., PNAS , 2005

cellulose degradation

Cell Cellulosomes Cellulose

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

>10 km

M EDLINE

SGD Saccharomyces Genome Database

The Interactive Fly

OMIM Online Mendelian Inheritance in Man

co-mentioning

NLP Natural Language Processing

[object Object],[object Object],[object Object],[object Object],[object Object]

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

intergenic distances

benchmarking

calibrate vs. gold standard

von Mering et al., Nucleic Acids Research , 2005

raw quality scores

probabilistic scores

integrate over orthologs

protein mode

von Mering et al., Nucleic Acids Research , 2005

COG mode

von Mering et al., Nucleic Acids Research , 2005

combine all evidence

Frishman et al., Modern Genome Annotation , 2009

small molecules

Kuhn et al., Nucleic Acids Research , 2008

metametabolomics

Acknowledgments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Data integration - Integration of functional associations using STRING

1. Data integration Integration of functional associations using STRING Lars Juhl Jensen

2. Jensen, Kuhn et al., Nucleic Acids Research , 2009

3. functional associations

4. confidence scores

5. cross-species integration

7. model organism databases

10. defining orthology

12. protein mode

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

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

16. genomic context

17. gene fusion

18. Korbel et al., Nature Biotechnology , 2004

19. conserved neighborhood

21. Korbel et al., Nature Biotechnology , 2004

22. bidirectional promoters

23. Korbel et al., Nature Biotechnology , 2004

24. phylogenetic profiles

25. Korbel et al., Nature Biotechnology , 2004

27. bacterial Cox assembly

28.

29. Banci et al., PNAS , 2005

30. Banci et al., PNAS , 2005

31. cellulose degradation

32.

33.

34.

35. Cell Cellulosomes Cellulose

36. experimental data

37. protein interactions

38. yeast two-hybrid

39. affinity purification

40. fragment complementation

41. Jensen & Bork, Science , 2008

42. genetic interactions

43. Beyer et al., Nature Reviews Genetics , 2007

44. BIND Biomolecular Interaction Network Database

45. BioGRID General Repository for Interaction Datasets

46. DIP Database of Interacting Proteins

48. MINT Molecular Interactions Database

49. HPRD Human Protein Reference Database

50. PDB Protein Data Bank

51. inferred associations

52. gene coexpression

53.

54. GEO Gene Expression Omnibus

55. expression compendia

56. curated knowledge

58. MIPS Munich Information center for Protein Sequences

59. Gene Ontology

61. Letunic & Bork, Trends in Biochemical Sciences , 2008

62. KEGG Kyoto Encyclopedia of Genes and Genomes

65. PID NCI-Nature Pathway Interaction Database

66. literature mining

69. SGD Saccharomyces Genome Database

70. The Interactive Fly

71. OMIM Online Mendelian Inheritance in Man

72. co-mentioning

73. NLP Natural Language Processing

74.

75.

76. easy in theory …

77. … but not in practice

78. many data types

79. not comparable

80. variable quality

81. many sources

82. different file formats

83. different gene identifiers

84. partially redundant

85. spread over 630 genomes

86. quality scores

87. reproducibility

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

89. intergenic distances

90.

91. benchmarking

92. calibrate vs. gold standard

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

94. raw quality scores

95. probabilistic scores

96. integrate over orthologs

97. protein mode

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

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

101. combine all evidence

102. Frishman et al., Modern Genome Annotation , 2009

103. small molecules

104. Kuhn et al., Nucleic Acids Research , 2008

105. metametabolomics

106.

107. larsjuhljensen