systems biology: large-scale biomedical data mining
TRANSCRIPT
Systems biologyLarge-scale biomedical data mining
Lars Juhl Jensen
Phase 1association networks
who?
protein networks
Jensen, Kuhn et al., Nucleic Acids Research, 2009
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
gene coexpression
protein interactions
Jensen & Bork, Science, 2008
genetic interactions
Beyer et al., Nature Reviews Genetics, 2007
curated knowledge
Letunic & Bork, Trends in Biochemical Sciences, 2008
>10 km
text mining
Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
co-mentioning
NLPNatural Language Processing
different formats
different names
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
Frishman et al., Modern Genome Annotation, 2009
Phase 2signaling networks
what?
phosphoproteomics
kinases are unknown
sequence motifs
machine-learning methods
Miller, Jensen et al., Science Signaling, 2008
peptide assays
Miller, Jensen et al., Science Signaling, 2008
automated pipeline
Miller, Jensen et al., Science Signaling, 2008
sequence specificity
no context
network context
Linding, Jensen, Ostheimer et al., Cell, 2007
Linding, Jensen, Ostheimer et al., Cell, 2007
>2x better accuracy
context is crucial
example
DNA damage response
Linding, Jensen, Ostheimer et al., Cell, 2007
small-scale validation
Linding, Jensen, Ostheimer et al., Cell, 2007
Phase 3dynamic networks
when?
cell-cycle regulation
microarray time courses
Gauthier et al., Nucleic Acids Research, 2007
protein interactions
temporal network
de Lichtenberg, Jensen et al., Science, 2005
de Lichtenberg, Jensen et al., Science, 2005
just-in-time assembly
de Lichtenberg, Jensen et al., Cell Cycle, 2007
evolutionary flexibility
individual genes
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
protein complexes
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
phosphorylation
co-evolution
Jensen, Jensen, de Lichtenberg et al., Nature, 2006
summary
data mining
specific predictions
systems properties
thank you!
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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