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Unraveling signal transduction networks through data integration
 

Unraveling signal transduction networks through data integration

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Minisymposium on Glycoanalysis and Glycochemistry, University of Copenhagen, Copenhagen, Denmark, October 26, 2009.

Minisymposium on Glycoanalysis and Glycochemistry, University of Copenhagen, Copenhagen, Denmark, October 26, 2009.

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  • Atlas of human kinases Atlases for phospho-binding proteins Atlases for model organisms Ubiquitination would be welcome

Unraveling signal transduction networks through data integration Unraveling signal transduction networks through data integration Presentation Transcript

  • Unraveling signal transduction networks through data integration Lars Juhl Jensen
  • the problem
  • phosphoproteomics
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • in vivo phosphosites
  • kinases are unknown
  • functions are unknown
  • sequence specificity
  • peptide assays
  • Miller, Jensen et al., Science Signaling , 2008
  • domain-specific
  • in vitro
  • no context
  • what could happen
  • not what does happen
  • machine-learning methods
  • sequence motifs
  • Miller, Jensen et al., Science Signaling , 2008
  • domain-specific
  • group-specific
  • no context
  • what could happen
  • not what does happen
  • in vitro
  • in vivo
  • context
  • co-activators
  • protein scaffolds
  • subcellular localization
  • spatial expression
  • temporal expression
  • association networks
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • the idea
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • the sequence motifs
  • NetPhorest
  • automated pipeline
  • Miller, Jensen et al., Science Signaling , 2008
  • data organization
  • Miller, Jensen et al., Science Signaling , 2008
  • compilation of datasets
  • redundancy reduction
  • training and evaluation
  • classifier selection
  • motif atlas
  •  
  • 179 kinases
  • 89 SH2 domains
  • 8 PTB domains
  • BRCT domains
  • WW domains
  • 14-3-3 proteins
  • use cases
  • Miller, Jensen et al., Science Signaling , 2008
  • the context network
  • guilt by association
  •  
  • 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
  • Korbel et al., Nature Biotechnology , 2004
  • 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
  • context network
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • the results
  • NetworKIN
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • benchmarking
  • Phospho.ELM
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • context is crucial
  • much context still missing
  • subcellular localization
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • ATM signaling
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • small-scale validation
  • ATM phosphorylates Rad50
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • Cdk1 phosphorylates 53BP1
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • high-throughput validation
  • multiple reaction monitoring
  • Linding, Jensen, Ostheimer et al., Cell , 2007
  • the future
  • new scoring scheme
  • two separate scores
  • one combined score
  • path length penalty
  • model organisms
  • S. cerevisiae
  • D. melanogaster
  • C. elegans
  • ( S. pombe )
  • other modifications
  • phosphatases
  • ubiquitylation
  • acetylation
  • glycosylation
  • Acknowledgments
    • NetPhorest.info
      • Rune Linding
      • Martin Lee Miller
      • Francesca Diella
      • Claus Jørgensen
      • Michele Tinti
      • Lei Li
      • Marilyn Hsiung
      • Sirlester A. Parker
      • Jennifer Bordeaux
      • Thomas Sicheritz-Pontén
      • Marina Olhovsky
      • Adrian Pasculescu
      • Jes Alexander
      • Stefan Knapp
      • Nikolaj Blom
      • Peer Bork
      • Shawn Li
      • Gianni Cesareni
      • Tony Pawson
      • Benjamin E. Turk
      • Michael B. Yaffe
      • Søren Brunak
    • STRING-DB.org
      • Christian von Mering
      • Michael Kuhn
      • Manuel Stark
      • Samuel Chaffron
      • Chris Creevey
      • Jean Muller
      • Tobias Doerks
      • Philippe Julien
      • Alexander Roth
      • Milan Simonovic
      • Jan Korbel
      • Berend Snel
      • Martijn Huynen
      • Peer Bork
    • NetworKIN.info
      • Rune Linding
      • Gerard Ostheimer
      • Heiko Horn
      • Martin Lee Miller
      • Francesca Diella
      • Karen Colwill
      • Jing Jin
      • Pavel Metalnikov
      • Vivian Nguyen
      • Adrian Pasculescu
      • Jin Gyoon Park
      • Leona D. Samson
      • Rob Russell
      • Peer Bork
      • Michael B. Yaffe
      • Tony Pawson
  • larsjuhljensen