systems biology: large-scale biomedical data mining
TRANSCRIPT
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Systems biologyLarge-scale biomedical data mining
Lars Juhl Jensen
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Phase 1association networks
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who?
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protein networks
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Jensen, Kuhn et al., Nucleic Acids Research, 2009
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genomic context
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gene fusion
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Korbel et al., Nature Biotechnology, 2004
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conserved neighborhood
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Korbel et al., Nature Biotechnology, 2004
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phylogenetic profiles
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Korbel et al., Nature Biotechnology, 2004
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gene coexpression
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protein interactions
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Jensen & Bork, Science, 2008
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genetic interactions
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Beyer et al., Nature Reviews Genetics, 2007
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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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text mining
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Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
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co-mentioning
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NLPNatural Language Processing
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different formats
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different names
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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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Frishman et al., Modern Genome Annotation, 2009
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Phase 2signaling networks
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what?
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phosphoproteomics
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kinases 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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automated pipeline
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Miller, Jensen et al., Science Signaling, 2008
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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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Linding, Jensen, Ostheimer et al., Cell, 2007
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>2x better accuracy
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context is crucial
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example
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DNA damage response
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Linding, Jensen, Ostheimer et al., Cell, 2007
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small-scale validation
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Linding, Jensen, Ostheimer et al., Cell, 2007
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Phase 3dynamic networks
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when?
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cell-cycle regulation
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microarray time courses
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Gauthier et al., Nucleic Acids Research, 2007
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protein interactions
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temporal network
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de Lichtenberg, Jensen et al., Science, 2005
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de Lichtenberg, Jensen et al., Science, 2005
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just-in-time assembly
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de Lichtenberg, Jensen et al., Cell Cycle, 2007
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evolutionary flexibility
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individual genes
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Jensen, Jensen, de Lichtenberg et al., Nature, 2006
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protein complexes
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Jensen, Jensen, de Lichtenberg et al., Nature, 2006
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phosphorylation
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co-evolution
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Jensen, Jensen, de Lichtenberg et al., Nature, 2006
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summary
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data mining
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specific predictions
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systems properties
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thank you!
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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– 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.ws– Sune Frankild– Heiko Horn– Evangelos Pafilis– Michael Kuhn– Nigel Brown– Reinhardt Schneider– Sean O’Donoghue
NetworKIN.info– 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
Cyclebase.org– Ulrik de Lichtenberg– Thomas Skøt Jensen– Nicholas Paul Gauthier– Rasmus Wernersson– Søren Brunak
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larsjuhljensen