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Network biology Large-scale biomedical data and text mining Lars Juhl Jensen
three parts
association networks
signaling networks
drug networks
Part 1 association 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 , 2009 O’Donoghue et al.,  Journal of Web Semantics , 2010
information extraction
co-mentioning
 
Part 2 signaling 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 3 drug 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
K i <10 µM for 11 of 20
cell assays
9 of 9 showed activity
Acknowledgments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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