unraveling signaling networks by data integration

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CPR Seminar, University of Copenhagen, Copenhagen, Denmark, February 6, 2009

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Unraveling signalingnetworks by data integration

Lars Juhl Jensen

promoter analysis

Jensen & Knudsen, Bioinformatics, 2000

genome visualization

Pedersen, Jensen et al., Journal of Molecular Biology, 2000

function prediction

Jensen, Gupta et al., Journal of Molecular Biology, 2002

data integration

Jensen & Bork, Drug Discovery Today: TARGETS, 2004

Gavin, Aloy et al., Nature, 2006

cell-cycle regulation

de Lichtenberg, Jensen et al., Science, 2005

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

drug repurposing

Campillos, Kuhn et al., Science, 2008

signaling networks

phosphoproteomics

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

in vivo phosphosites

kinases are unknown

peptide assays

Miller, Jensen et al., Science Signaling, 2008

kinase-specific

in vitro

no context

machine-learning methods

Phospho.ELM

Miller, Jensen et al., Science Signaling, 2008

kinase-specific

no context

context

association networks

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

NetworKIN

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

sequence motifs

NetPhorest

Miller, Jensen et al., Science Signaling, 2008

data organization

Miller, Jensen et al., Science Signaling, 2008

automated pipeline

compilation of datasets

redundancy reduction

training and evaluation

classifier selection

motif atlas

179 kinases

93 SH2 domains

8 PTB domains

BRCT domains

WW domains

14-3-3 proteins

comparison

Miller, Jensen et al., Science Signaling, 2008

association networks

STRING

functional associations

630 genomes

genomic context

gene fusion

Korbel et al., Nature Biotechnology, 2004

conserved neighborhood

Korbel et al., Nature Biotechnology, 2004

phylogenetic profiles

Korbel et al., Nature Biotechnology, 2004

primary experimental data

protein interactions

Jensen & Bork, Science, 2008

gene coexpression

literature mining

curated knowledge

Letunic & Bork, Trends in Biochemical Sciences, 2008

benchmarking

von Mering et al., Nucleic Acids Research, 2005

transfer by orthology

combine all evidence

Frishman et al., Modern Genome Annotation, 2009

small molecules

STITCH

Kuhn et al., Nucleic Acids Research, 2008

kinase inhibitor screens

Fedorov et al., PNAS, 2007

design optimal experiments

multiple reaction monitoring

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

high-throughput validation

NetworKIN predictions

augmented browsing

Reflect

Acknowledgments

NetworKIN.info– 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

STITCH.embl.de– Michael Kuhn– Christian von Mering– Monica Campillos– Peer Bork

NetPhorest.info– 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– Philippe Julien– Tobias Doerks– Jan Korbel– Berend Snel– Martijn Huynen– Peer Bork

Reflect.ws– Sean O’Donoghue– Evangelos Pafilis– Heiko Horn– Michael Kuhn– Nigel Brown– Reinhardt Schneider

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