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Unraveling signaling networks by large-scale data integration

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Lars Juhl Jensen
Lars Juhl Jensen

BioRange, Lunteren, Netherlands, March 17-18, 2009

TechnologieSpirituel
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Unraveling signaling networks by large-scale data integration Lars Juhl Jensen
 
 
 
 
the problem
phosphoproteomics
Linding, Jensen, Ostheimer et al., Cell , 2007
in vivo phosphosites
kinases are unknown
peptide assays
Miller, Jensen et al., Science Signaling , 2008
machine-learning methods
sequence motifs
Miller, Jensen et al., Science Signaling , 2008
kinase-specific
sequence specificity
no context
what a kinase could do
not what it actually does
context
co-activators
scaffolders
localization
expression
association networks
Linding, Jensen, Ostheimer et al., Cell , 2007
the good idea
Linding, Jensen, Ostheimer et al., Cell , 2007
a lot of work
the sequence motifs
NetPhorest
Miller, Jensen et al., Science Signaling , 2008
data organization
Miller, Jensen et al., Science Signaling , 2008
automated pipeline
compilation of datasets
redundancy reduction
training and evaluation
classifier selection
motif atlas
 
179 kinases
93 SH2 domains
8 PTB domains
BRCT domains
WW domains
14-3-3 proteins
phosphatases
model organisms
biological insights
docking domains
Miller, Jensen et al., Science Signaling , 2008
disease-related kinases
Miller, Jensen et al., Science Signaling , 2008
the context network
STRING
Jensen, Kuhn et al., Nucleic Acids Research , 2009
functional associations
data integration
primary experimental data
protein interactions
Jensen & Bork, Science , 2008
gene coexpression
 
genomic context methods
gene fusion
Korbel et al., Nature Biotechnology , 2004
conserved neighborhood
Korbel et al., Nature Biotechnology , 2004
literature mining
 
curated knowledge
Letunic & Bork, Trends in Biochemical Sciences , 2008
too easy …
… to be true
different formats
different identifiers
variable quality
spread over 630 genomes
parsers
thesaurus
raw quality scores
benchmarking
von Mering et al., Nucleic Acids Research , 2005
transfer by orthology
von Mering et al., Nucleic Acids Research , 2005
combine all evidence
visualize
Frishman et al., Modern Genome Annotation , 2009
the results
NetworKIN
 
benchmarking
Linding, Jensen, Ostheimer et al., Cell , 2007
DNA damage response
Linding, Jensen, Ostheimer et al., Cell , 2007
small-scale validation
ATM phosphorylates Rad50
Linding, Jensen, Ostheimer et al., Cell , 2007
high-throughput validation
multiple reaction monitoring
Linding, Jensen, Ostheimer et al., Cell , 2007
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STRING & STITCH : Network integration of heterogeneous data
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Biomedical text mining: Automatic processing of unstructured text
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Medical network analysis: Linking diseases and genes through data and text mi...
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Network Biology: A crash course on STRING and Cytoscape
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Cellular networks
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Cellular Network Biology: Large-scale integration of data and text
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Statistics on big biomedical data: Methods and pitfalls when analyzing high-t...
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STRING & related databases: Large-scale integration of heterogeneous data
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Tagger: Rapid dictionary-based named entity recognition
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Medical text mining: Linking diseases, drugs, and adverse reactions
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Network biology: Large-scale integration of data and text
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Medical data and text mining: Linking diseases, drugs, and adverse reactions
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Network biology: Large-scale integration of data and text
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Biomarker bioinformatics: Network-based candidate prioritization
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The Art of Counting: Scoring and ranking co-occurrences in literature
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Text-mining-based retrieval of protein networks
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Unraveling signaling networks by large-scale data integration