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Protein interaction networks from yeast to human Lars Juhl Jensen EMBL Heidelberg
Current Opinion in Structural Biology, 2005
STRING
 
integrate diverse evidence
functional interactions
Bork et al., Current Opinion in Structural Biology, 2005
hundreds of proteomes
evolution
 
 
statistics
(the original sin)
prokaryotes
genomic context methods
gene fusion
 
gene neighborhood
 
phylogenetic profiles
 
 
 
 
Cell Cellulosomes Cellulose
eukaryotes
integrate diverse datasets
Jensen et al., Drug Discovery Today: Targets, 2004
curated knowledge
MIPS Munich Information center for Protein Sequences
KEGG Kyoto Encyclopedia of Genes and Genomes
STKE Signal Transduction Knowledge Environment
Reactome
literature mining
co-mentioning
NLP Natural Language Processing
M EDLINE
SGD Saccharomyces Genome Database
The Interactive Fly
OMIM Online Mendelian Inheritance in Man
primary experimental data
microarray expression data
GEO Gene Expression Omnibus
physical protein interactions
BIND Biomolecular Interaction Network Database
MINT Molecular Interactions Database
GRID General Repository for Interaction Datasets
DIP Database of Interacting Proteins
HPRD Human Protein Reference Database
problems
many sources
(different gene identifiers)
many types of evidence
questionable quality
not directly comparable
spread over many species
huge synonyms lists
calculate raw quality scores
calibrate vs. gold standard
KEGG Kyoto Encyclopedia of Genes and Genomes
von Mering et al., Nucleic Acids Research, 2005
transfer based on orthology
combine all evidence
Bork et al., Current Opinion in Structural Biology, 2005
Networ-Kin™ Phospho-peptide data (from MS) Predict the kinase class (NetPhosK and Scansite)
the human interactome
yeast two-hybrid
1936 13 4 4 1385 65 18465 Stelzl  et al. Rual  et al. Small-scale studies
32 0 3 4 18 4 23 Stelzl  et al. Rual  et al. Small-scale studies
62 8 39 Small-scale studies Stelzl  et al. Rual  et al. 852 17 473 432 69 260
3.5% and 21% sensitivity
in a couple of years
the human interactome
100% = 1/5?
the yeast interactome
five years ago
yeast two-hybrid
1150 117 117 72 4053 118 4469 Uetz  et al. Ito  et al. Small-scale studies
162 53 34 72 180 29 338 Uetz  et al. Ito  et al. Small-scale studies
511 189 616 Small-scale studies Uetz  et al. Ito  et al. 439 178 759 897 190 1347
19% and 12% sensitivity
three years ago
complex purification and MS
14186 784 1178 287 19492 230 3475 Gavin  et al. Ho  et al. Small-scale studies
2341 125 656 287 2725 42 149 Gavin  et al. Ho  et al. Small-scale studies
4431 1465 5041 Small-scale studies Gavin  et al. Ho  et al. 14913 1071 632 8047 517 746
63% and 41% sensitivity
today
combining all available data
scoring and filtering
 
de Lichtenberg et al., Science, 2005
de Lichtenberg et al., Science, 2005
de Lichtenberg et al., Science, 2005
de Lichtenberg et al., Science, 2005
de Lichtenberg et al., Science, 2005
the challenge
how to get from here …
1936 13 4 4 1385 65 18465 Stelzl  et al. Rual  et al. Small-scale studies
…  to there …
de Lichtenberg et al., Science, 2005
yeast two-hybrid
complex purification and MS
scoring and filtering
Acknowledgments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thank you!

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Protein interaction networks from yeast to human