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Systematic discovery of phosphorylation networks - Combining linear motifs and protein interactions

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Lars Juhl Jensen
Lars Juhl Jensen

Munich, Germany, November 7, 2007

Technologie
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Systematic discovery of phosphorylation networks Combining linear motifs and protein interactions Lars Juhl Jensen EMBL Heidelberg
Lars Juhl Jensen
 
 
promoter analysis
 
genome visualization
 
protein function prediction
 
 
 
data integration
 
dynamic interactions
 
prediction of interactions
http://string.embl.de
prediction of interactions
http://networkin.info
the starting point
phosphoproteomics
mass spectrometry
 
phosphorylation sites
in vivo
kinases are unknown
HTP kinase assays
in vitro
no context
what a kinase could do
not what it actually does
computational methods
sequence motifs
 
kinase families
phosphorylation sites
overprediction
no context
what a kinase could do
not what it actually does
in vitro
in vivo
context
localization
expression
co-activators
scaffolders
protein networks
 
the idea
mass spectrometry
 
phosphorylation sites
sequence motifs
 
kinase families
protein networks
 
context
in vitro
in vivo
“ shake and bake”
 
NetworKIN
the context network
STRING
functional interactions
373 genomes
 
genomic context methods
gene neighborhood
 
gene fusion
 
phylogenetic profiles
 
primary experimental data
protein interactions
 
genetic interactions
 
gene coexpression
 
literature mining
 
curated knowledge
 
many sources
different formats
different gene identifiers
redundancy
variable quality
spread over many species
benchmarking
 
transfer by orthology
 
combine all evidence
 
the results
 
7797 predictions
1790 substrates
69 kinases
 
benchmarking
Phospho.ELM
 
2.5-fold better accuracy
context is crucial
localization
 
visualization
 
ATM signaling
 
small-scale validation
ATM phosphorylates Rad50
 
Cdk1 phosphorylates 53BP1
 
high-throughput validation
multiple reaction monitoring
 
the future
more sequence motifs
in vivo
in vitro
automatic pipeline
http://netphorest.info
data organization
 
benchmarking
 
selection
 
179 kinases
89 SH2 domains
8 PTB domains
upstream signaling
downstream signaling
ordered signaling events
signaling pathways
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],[object Object],[object Object],[object Object],[object Object]
 

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