systematic discovery of phosphorylation networks - combining linear motifs and protein interactions
DESCRIPTION
Munich, Germany, November 7, 2007TRANSCRIPT
Systematic discovery ofphosphorylation 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
The NetworKIN method– Rune Linding
– Gerard Ostheimer
– Francesca Diella
– Karen Colwill
– Jing Jin
– Pavel Metalnikov
– Vivian Nguyen
– Adrian Pasculescu
– Jin Gyoon Park
– Leona D. Samson
– Rob Russell
– Peer Bork
– Michael Yaffe
– Tony Pawson
The STRING database– Christian von Mering
– Michael Kuhn
– Berend Snel
– Martijn Huynen
– Samuel Chaffron
– Peer Bork
• The NetPhorest method– Martin Lee Miller– Rune Linding– Nikolaj Blom– Søren Brunak