Prediction of protein–small molecule networks through large-scale data integration Lars Juhl Jensen
Prediction of protein-small molecule networks through large-scale data integration
Jul 09, 2015
KU Bioinformatics Workshop, University of Copenhagen, Copenhagen, Denmark, January 26, 2009
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Prediction of protein–small moleculenetworks through large-scale data integration
Lars Juhl Jensen
function prediction
cell-cycle regulation
de Lichtenberg & Jensen et al., Science, 2005
data integration
the problem
new uses for old drugs
drug–drug network
shared target(s)
chemical similarity
Tanimoto coefficients
Campillos & Kuhn et al., Science, 2008
Campillos & Kuhn et al., Science, 2008
similar drugs share targets
only trivial predictions
the idea
chemical perturbations
phenotypic readouts
drug treatment
side effects
the implementation
information on side effects
package inserts
Campillos & Kuhn et al., Science, 2008
text mining
side-effect ontology
backtracking
Campillos & Kuhn et al., Science, 2008
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
reference set
drug–target pairs
Campillos & Kuhn et al., Science, 2008
drug–drug pairs
score bins
benchmark
Campillos & Kuhn et al., Science, 2008
fit calibration function
Campillos & Kuhn et al., Science, 2008
probabilistic scores
the results
drug–drug network
ATC codes
Campillos & Kuhn et al., Science, 2008
categorization
Campillos & Kuhn et al., Science, 2008
Campillos & Kuhn et al., Science, 2008
Campillos & Kuhn et al., Science, 2008
map onto score space
Campillos & Kuhn et al., Science, 2008
the experiments
20 drug–drug relations
in vitro binding assays
Campillos & Kuhn et al., Science, 2008
Campillos & Kuhn et al., Science, 2008
Campillos & Kuhn et al., Science, 2008
Ki<10 µM for 11 of 20
cell assays
Campillos & Kuhn et al., Science, 2008
9 of 9 showed activity
the bigger picture
STITCH
protein–chemical network
Kuhn et al., Nucleic Acids Research, 2008
primary experimental data
activity screens
Fedorov et al., PNAS, 2007
protein interactions
Jensen & Bork, Science, 2008
gene coexpression
genomic context
Korbel et al., Nature Biotechnology, 2004
literature mining
curated knowledge
Letunic & Bork, Trends in Biochemical Sciences, 2008
different formats
different identifiers
different reliability
benchmarking
von Mering et al., Nucleic Acids Research, 2005
373 genomes
Jensen et al., Nucleic Acids Research, 2008
transfer by orthology
combine all evidence
Kuhn et al., Nucleic Acids Research, 2008
Acknowledgments
Monica Campillos
Michael Kuhn
Christian von Mering
Anne-Claude Gavin
Peer Bork
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