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Network biologyLarge-scale biomedical data and text mining
Lars Juhl Jensen
three parts
association networks
signaling networks
drug networks
Part 1association networks
guilt by association
STRING
Szklarczyk, Franceschini et al., Nucleic Acids Research, 2011
>1100 genomes
genomic context
gene fusion
Korbel et al., Nature Biotechnology, 2004
experimental data
protein interactions
Jensen & Bork, Science, 2008
curated knowledge
pathways
Letunic & Bork, Trends in Biochemical Sciences, 2008
many data types
many databases
different formats
different identifiers
variable quality
quality scores
von Mering et al., Nucleic Acids Research, 2005
calibrate vs. gold standard
von Mering et al., Nucleic Acids Research, 2005
orthology transfer
missing most of the data
>10 km
too much to read
computer
as smart as a dog
teach it specific tricks
named entity recognition
identify the concepts
proteins
comprehensive lexicon
orthographic variation
“black list”
Reflect
augmented browsing
Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009O’Donoghue et al., Journal of Web Semantics, 2010
information extraction
co-mentioning
Part 2signaling networks
phosphoproteomics
in vivo phosphosites
kinases are unknown
sequence specificity
Miller, Jensen et al., Science Signaling, 2008
NetPhorest
automated pipeline
Miller, Jensen et al., Science Signaling, 2008
protein-specific
no context
co-activators
protein scaffolds
localization
expression
association network
Linding, Jensen, Ostheimer et al., Cell, 2007
NetworKIN
Linding, Jensen, Ostheimer et al., Cell, 2007
Part 3drug networks
drug repurposing
drug–drug network
chemical similarity
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
manual validation
SIDER
side-effect similarity
Campillos & Kuhn et al., Science, 2008
combined similarity
Campillos & Kuhn et al., Science, 2008
categorization
Campillos & Kuhn et al., Science, 2008
20 drug–drug pairs
in vitro binding assays
Ki<10 µM for 11 of 20
cell assays
9 of 9 showed activity
Acknowledgments
ReflectSune Frankild
Heiko Horn
Evangelos Pafilis
Michael Kuhn
Reinhardt Schneider
Sean O’Donoghue
Side effectsMonica Campillos
Michael Kuhn
Anne-Claude Gavin
Peer Bork
STRINGDamian Szklarczyk
Andrea Franceschini
Michael Kuhn
Milan Simonovic
Alexander Roth
Pablo Minguez
Tobias Doerks
Manuel Stark
Jean Muller
Peer Bork
Christian von Mering
NetworKINHeiko Horn
Martin Lee Miller
Gerard Ostheimer
Francesca Diella
Claus Jørgensen
Rob Russell
Peer Bork
Benjamin Turk
Michael Yaffe
Tony Pawson
Rune Linding
larsjuhljensen