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Network biologyA basis for large-scale biomedical data mining
Lars Juhl Jensen
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sequence analysis
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Jensen, Gupta et al., Journal of Molecular Biology, 2002
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data mining
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de Lichtenberg, Jensen et al., Science, 2005
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data mining
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text mining
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Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
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signaling networks
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phosphoproteomics
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Linding, Jensen, Ostheimer et al., Cell, 2007
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in vivo phosphosites
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kinases are unknown
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sequence motifs
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Miller, Jensen et al., Science Signaling, 2008
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NetPhorest
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data organization
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Miller, Jensen et al., Science Signaling, 2008
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automated pipeline
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Miller, Jensen et al., Science Signaling, 2008
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motif atlas
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sequence specificity
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no context
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network context
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Linding, Jensen, Ostheimer et al., Cell, 2007
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guilt by association
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STRING
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630 genomes
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computational predictions
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gene fusion
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Korbel et al., Nature Biotechnology, 2004
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experimental data
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physical interactions
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Jensen & Bork, Science, 2008
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gene coexpression
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curated knowledge
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Letunic & Bork, Trends in Biochemical Sciences, 2008
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>10 km
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literature mining
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Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
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not comparable
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confidence scores
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von Mering et al., Nucleic Acids Research, 2005
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cross-species integration
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von Mering et al., Nucleic Acids Research, 2005
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association network
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Linding, Jensen, Ostheimer et al., Cell, 2007
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integrate with motifs
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NetworKIN
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Linding, Jensen, Ostheimer et al., Cell, 2007
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>2x better accuracy
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drug repositioning
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new uses for old drugs
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drug–drug network
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shared target(s)
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chemical similarity
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Campillos & Kuhn et al., Science, 2008
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similar drugs share targets
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Campillos & Kuhn et al., Science, 2008
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only trivial predictions
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phenotypic similarity
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chemical perturbations
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phenotypic readouts
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drug treatment
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side effects
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no database
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package inserts
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Campillos & Kuhn et al., Science, 2008
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text mining
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side-effect ontology
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Campillos & Kuhn et al., Science, 2008
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manual validation
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SIDER
Kuhn et al., Molecular Systems Biology, 2010
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side-effect correlations
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Campillos & Kuhn et al., Science, 2008
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GSC weighting
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side-effect frequencies
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Campillos & Kuhn et al., Science, 2008
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raw similarity score
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Campillos & Kuhn et al., Science, 2008
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p-values
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Campillos & Kuhn et al., Science, 2008
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side-effect similarity
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chemical similarity
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Campillos & Kuhn et al., Science, 2008
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confidence scores
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drug–drug network
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Campillos & Kuhn et al., Science, 2008
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categorization
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Campillos & Kuhn et al., Science, 2008
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experimental validation
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20 drug–drug pairs
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in vitro binding assays
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Ki<10 µM for 11 of 20
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cell assays
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9 of 9 showed activity
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work in progress
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link side-effects to targets
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direct target prediction
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thank you!NetPhorest
– 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● Christian von Mering● Damian Szklarczyk● 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
Reflect● Sune Frankild● Heiko Horn● Evangelos Pafilis● Michael Kuhn● Nigel Brown● Reinhardt Schneider● Sean O’Donoghue
NetworKIN● Rune Linding● Heiko Horn● Gerard Ostheimer● 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
Side effect● Monica Campillos● Michael Kuhn● Christian von Mering● Anne-Claude Gavin● Peer Bork
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