from phosphoproteomics to signaling networks
DESCRIPTION
Orbitrap User Meeting, University of Southern Denmark, Odense, Denmark, December 2, 2009.TRANSCRIPT
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From phosphoproteomicsto signaling networks
Lars Juhl Jensen
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Orbitrap
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in vivo phosphosites
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kinases are unknown
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functions are unknown
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sequence motifs
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machine-learning methods
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Miller, Jensen et al., Science Signaling, 2008
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peptide assays
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Miller, Jensen et al., Science Signaling, 2008
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domain-specific
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group-specific
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no context
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in vitro
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in vivo
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context
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co-activators
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protein scaffolds
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localization
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expression
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NetworKIN
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Linding, Jensen, Ostheimer et al., Cell, 2007
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functional associations
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Jensen, Kuhn et al., Nucleic Acids Research, 2009
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data integration
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pathways
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Letunic & Bork, Trends in Biochemical Sciences, 2008
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protein interactions
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Jensen & Bork, Science, 2008
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gene coexpression
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genomic context methods
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Korbel et al., Nature Biotechnology, 2004
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literature mining
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different formats
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different identifiers
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variable quality
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not comparable
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spread over 630 genomes
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confidence scores
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von Mering et al., Nucleic Acids Research, 2005
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transfer by orthology
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von Mering et al., Nucleic Acids Research, 2005
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Linding, Jensen, Ostheimer et al., Cell, 2007
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does it work?
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Linding, Jensen, Ostheimer et al., Cell, 2007
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context is crucial
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much context missing
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many motifs missing
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NetPhorest
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automated pipeline
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Miller, Jensen et al., Science Signaling, 2008
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data organization
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Miller, Jensen et al., Science Signaling, 2008
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compilation of datasets
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redundancy reduction
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training and evaluation
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classifier selection
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motif atlas
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179 kinases
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89 SH2 domains
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8 PTB domains
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BRCT domains
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WW domains
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14-3-3 proteins
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use case
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cell-cycle kinases
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Olsen et al., Science Signaling, 2009
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coming soon(ish)
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new web interface
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new scoring scheme
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path length penalty
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Linding, Jensen, Ostheimer et al., Cell, 2007
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model organisms
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S. cerevisiae
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D. melanogaster
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C. elegans
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other modifications
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phosphatases
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acetylation
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ubiquitylation
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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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larsjuhljensen