combining sequence motifs and protein interactions to unravel complex phosphorylation networks
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Combining sequence motifs and protein interactions to unravel complex phosphorylation networks
Lars Juhl Jensen
the problem
phosphoproteomics
Linding, Jensen, Ostheimer et al., Cell, 2007
in vivo phosphosites
kinases are unknown
functions are unknown
sequence specificity
peptide assays
Miller, Jensen et al., Science Signaling, 2008
domain-specific
in vitro
no context
what could happen
not what does happen
machine-learning methods
sequence motifs
Miller, Jensen et al., Science Signaling, 2008
domain-specific
group-specific
no context
what could happen
not what does happen
in vitro
in vivo
context
co-activators
protein scaffolds
subcellular localization
spatial expression
temporal expression
association networks
Linding, Jensen, Ostheimer et al., Cell, 2007
the idea
Linding, Jensen, Ostheimer et al., Cell, 2007
the sequence motifs
NetPhorest
automated pipeline
Miller, Jensen et al., Science Signaling, 2008
data organization
Miller, Jensen et al., Science Signaling, 2008
compilation of datasets
redundancy reduction
training and evaluation
classifier selection
motif atlas
179 kinases
89 SH2 domains
8 PTB domains
BRCT domains
WW domains
14-3-3 proteins
use cases
Miller, Jensen et al., Science Signaling, 2008
the context network
NetworKIN
Linding, Jensen, Ostheimer et al., Cell, 2007
STRING
Jensen, Kuhn et al., Nucleic Acids Research, 2009
protein interactions
Jensen & Bork, Science, 2008
gene coexpression
localization
Linding, Jensen, Ostheimer et al., Cell, 2007
benchmarking
Phospho.ELM
Linding, Jensen, Ostheimer et al., Cell, 2007
2.5-fold better accuracy
the experiments
ATM signaling
Linding, Jensen, Ostheimer et al., Cell, 2007
Linding, Jensen, Ostheimer et al., Cell, 2007
small-scale validation
ATM phosphorylates Rad50
Linding, Jensen, Ostheimer et al., Cell, 2007
high-throughput validation
multiple reaction monitoring
Linding, Jensen, Ostheimer et al., Cell, 2007
the future
new scoring scheme
two separate scores
one combined score
path length penalty
model organisms
S. cerevisiae
D. melanogaster
C. elegans
(S. pombe)
other modifications
phosphatases
ubiquitylation
F-box proteins
acetylation
AcknowledgmentsNetPhorest.info
– Rune Linding– Martin Lee Miller– Francesca Diella– Claus Jørgensen– Michele Tinti– Lei Li– Marilyn Hsiung– Sirlester A. Parker– Jennifer Bordeaux– Thomas Sicheritz-Pontén– Marina Olhovsky– Adrian Pasculescu– Jes Alexander– Stefan Knapp– Nikolaj Blom– Peer Bork– Shawn Li– Gianni Cesareni– Tony Pawson– Benjamin E. Turk– Michael B. Yaffe– Søren Brunak
STRING.embl.de– 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
NetworKIN.info– Rune Linding– Gerard Ostheimer– Heiko Horn– Martin Lee Miller– 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
larsjuhljensen
Thank you
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