From phosphoproteomics to signaling networks

From phosphoproteomicsto signaling networks

Lars Juhl Jensen

Orbitrap

in vivo phosphosites

kinases are unknown

functions are unknown

sequence motifs

machine-learning methods

Miller, Jensen et al., Science Signaling, 2008

peptide assays

Miller, Jensen et al., Science Signaling, 2008

domain-specific

group-specific

no context

in vitro

in vivo

context

co-activators

protein scaffolds

localization

expression

NetworKIN

Linding, Jensen, Ostheimer et al., Cell, 2007

functional associations

Jensen, Kuhn et al., Nucleic Acids Research, 2009

data integration

pathways

Letunic & Bork, Trends in Biochemical Sciences, 2008

protein interactions

Jensen & Bork, Science, 2008

gene coexpression

genomic context methods

Korbel et al., Nature Biotechnology, 2004

literature mining

different formats

different identifiers

variable quality

not comparable

spread over 630 genomes

confidence scores

von Mering et al., Nucleic Acids Research, 2005

transfer by orthology

von Mering et al., Nucleic Acids Research, 2005

Linding, Jensen, Ostheimer et al., Cell, 2007

does it work?

Linding, Jensen, Ostheimer et al., Cell, 2007

context is crucial

much context missing

many motifs missing

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 case

cell-cycle kinases

Olsen et al., Science Signaling, 2009

coming soon(ish)

new web interface

new scoring scheme

path length penalty

Linding, Jensen, Ostheimer et al., Cell, 2007

model organisms

S. cerevisiae

D. melanogaster

C. elegans

other modifications

phosphatases

acetylation

ubiquitylation

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-DB.org– 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 B. Yaffe– Tony Pawson

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