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