network medicine - integrating drugs, targets, diseases and side-effects
DESCRIPTION
LEO Pharma, Ballerup, Denmark, November 5, 2008TRANSCRIPT
Lars Juhl Jensen
Network medicineIntegrating drugs, targets, diseases and side-effects
Lars Juhl Jensen
Network medicineIntegrating drugs, targets, diseases and side-effects
Lars Juhl Jensen
Network medicineIntegrating drugs, targets, diseases and side-effects
what went wrong?
phase 0
before you do anything
a good problem
a good idea
dynamics of complexes
microarray data
protein interactions
de Lichtenberg, Jensen, et al., Science, 2005
phosphorylation networks
mass spectrometry data
sequence motifs
functional associations
Linding, Jensen, Ostheimer et al., Cell, 2007
Linding, Jensen, Ostheimer et al., Cell, 2007
the problem
new uses for old drugs
drug–drug network
shared target(s)
chemical similarity
Tanimoto coefficients
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
text mining
side-effect ontology
backtracking
side-effect correlations
GSC weighting
side-effect frequencies
raw similarity score
p-values
side-effect similarity
chemical similarity
reference set
drug–target pairs
drug–drug pairs
score bins
benchmark
fit calibration function
probabilistic scores
the results
drug–drug network
ATC codes
categorization
map onto score space
the experiments
20 drug–drug relations
in vitro binding assays
Ki<10 µM for 11 of 20
cell assays
9 of 9 showed activity
the big picture
STITCH
protein–chemical network
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
Acknowledgments
Monica Campillos
Michael Kuhn
Christian von Mering
Anne-Claude Gavin
Peer Bork
http://larsjuhljensen.wordpress.com