The document discusses the integration of heterogeneous biological data sources, including genomes, proteins, and small molecules, emphasizing their varying formats and identifiers. It highlights the challenges in data comparison and quality, as well as the importance of advanced methods in natural language processing for extracting relationships from literature. Various databases and methodologies for gene interactions, expression, and pathways are reviewed to enhance data accessibility for both humans and computational systems.

1. Integration of heterogeneous data Lars Juhl Jensen

6. data mining

7. text mining

8. interaction networks

10. Kuhn et al., Nucleic Acids Research , 2010

11. parts lists

12. 630 genomes

13. 2.5 million proteins

14. ~74,000 small molecules

15. many databases

16. different formats

17. model organism databases

18. Ensembl

19. RefSeq

20. PubChem

21. genomic context

22. gene fusion

23. Korbel et al., Nature Biotechnology , 2004

24. conserved neighborhood

25. operons

26. Korbel et al., Nature Biotechnology , 2004

27. bidirectional promoters

28. Korbel et al., Nature Biotechnology , 2004

29. phylogenetic profiles

30. Korbel et al., Nature Biotechnology , 2004

31. experimental data

32. gene coexpression

34. protein interactions

35. Jensen & Bork, Science , 2008

36. genetic interactions

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

38. small molecule interactions

39. in vitro binding assays

40. cellular activity assays

41. many databases

42. GEO Gene Expression Omnibus

43. BIND Biomolecular Interaction Network Database

44. BioGRID General Repository for Interaction Datasets

45. DIP Database of Interacting Proteins

46. IntAct

47. MINT Molecular Interactions Database

48. HPRD Human Protein Reference Database

49. PDB Protein Data Bank

50. BindingDB

51. CTD Comparative Toxicogenomics Database

52. DrugBank

53. GLIDA GPCR-Ligand Database

54. MATADOR

55. PDSP K i Psycoactive Drug Screening Program

56. PharmGKB Pharmacogenomics Knowledge Base

57. different formats

58. different identifiers

59. partially redundant

60. Campillos & Kuhn et al., Science , 2008

61. curated knowledge

62. complexes

63. pathways

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

65. many databases

66. Gene Ontology

67. MIPS Munich Information center for Protein Sequences

68. KEGG Kyoto Encyclopedia of Genes and Genomes

69. MetaCyc

70. Reactome

71. PID NCI-Nature Pathway Interaction Database

72. high confidence

73. different formats

74. different identifiers

75. partially redundant

76. literature mining

77. >10 km

78. human readable

79. not computer readable

80. different names

81. text corpus

82. M EDLINE

83. SGD Saccharomyces Genome Database

84. The Interactive Fly

85. OMIM Online Mendelian Inheritance in Man

86. thesaurus

87. co-mentioning

88. statistical methods

89. NLP Natural Language Processing

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

92. restricted access

93. Reflect

94. augmented browsing

95. Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology , 2009

96. integration

97. the easy problems

98. many databases

99. different formats

100. different identifiers

101. partially redundant

102. parsers

103. thesaurus

104. book keeping

105. the hard problems

106. many data types

107. not comparable

108. variable quality

109. raw quality scores

110. intergenic distances

111. Korbel et al., Nature Biotechnology , 2004

112. correlations

114. reproducibility

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

116. score calibration

117. gold standard

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

119. spread over 630 genomes

120. transfer by orthology

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

122. two modes

123. COG mode

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

125. protein mode

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

127. combine all evidence

128. P = 1-(1-P 1 )(1-P 2 )(1-P 3 ) …

129. visualize

130. Kuhn et al., Nucleic Acids Research , 2010

131. access

132. access for humans

133. web interfaces

137. access for computers

138. web services

139. REST Representational State Transfer

140. SOAP Simple Object Access Protocol

141. Acknowledgments STITCH Michael Kuhn Damian Szklarczyk Andrea Franceschini Monica Campillos Christian von Mering Lars Juhl Jensen Andreas Beyer Peer Bork Reflect Sean O’Donoghue Heiko Horn Sune Frankild Evangelos Pafilis Michael Kuhn Nigel Brown Reinhardt Schneider STRING Christian von Mering 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

142. larsjuhljensen