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Exploring proteins, chemicals and their interactions with STRING and STITCH
 

Exploring proteins, chemicals and their interactions with STRING and STITCH

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MPI, Dresden, 18.12.2007

MPI, Dresden, 18.12.2007

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    Exploring proteins, chemicals and their interactions with STRING and STITCH Exploring proteins, chemicals and their interactions with STRING and STITCH Presentation Transcript

    • Exploring proteins, chemicals and their interactions with STRING and STITCH Michael Kuhn EMBL Heidelberg
    • my usual diet work: drugs, proteins, side effects
    • today intro: interactions small examples the databases: STRING and STITCH larger example: NetworKIN
    • STRING: version 7 interactions of proteins STITCH: version 1 interactions of proteins and chemicals
    • interactions of proteins and chemicals
    • example Tryptophan synthase beta chain E. Coli K12
    • example aspirin Homo sapiens
    • content (STRING 7)
    • 373 genomes (only completely sequenced genomes)
    • 1.5 million genes (not proteins)
    • 68,000 chemicals (including 2200 drugs)
    • many sources of interactions
    • genomic context
    • gene neighborhood
    • gene fusion
    • phylogenetic profiles
    • curated knowledge
    • experimental evidence T
    • co-expression GEO: Gene Expression Omnibus
    • experimental databases
    • literature
    • variable quality different “raw scores”
    • benchmarking calibrate against “gold standard” (KEGG)
    • probabilistic scores e.g. “70% chance for an assocation”
    • combine all evidence
    • Bayesian scoring scheme
    • e.g.: two scores of 0.7 combined probability: ?
    • e.g.: two scores of 0.7 combined probability: 0.91 1- (1-0.7) 2 = 0.91
    • evidence spread over many species
    • evidence transfer
    • transfer by orthology (or “fuzzy orthology”)
    • von Mering et al., Nucleic Acids Research, 2005
    • von Mering et al., Nucleic Acids Research, 2005
    • two modes
    • proteins mode
    • von Mering et al., Nucleic Acids Research, 2005
    • maximum specificity lower coverage information will be relevant for selected species
    • COG mode “clusters of orthologous groups”
    • von Mering et al., Nucleic Acids Research, 2005
    • higher coverage lower specificity includes all available evidence some orthologous groups are too large to be meaningful
    • a real application Resource Systematic Discovery of In Vivo Phosphorylation Networks Rune Linding,1,2,7,* Lars Juhl Jensen,3,7 Gerard J. Ostheimer,2,4,7 Marcel A.T.M. van Vugt,2,5 Claus Jørgensen,1 Ioana M. Miron,1 Francesca Diella,3 Karen Colwill,1 Lorne Taylor,1 Kelly Elder,1 Pavel Metalnikov,1 Vivian Nguyen,1 Adrian Pasculescu,1 Jing Jin,1 Jin Gyoon Park,1 Leona D. Samson,4 James R. Woodgett,1 Robert B. Russell,3 Peer Bork,3,6,* Michael B. Yaffe,2,* and Tony Pawson1,* 1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada 2 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, USA 3 European Molecular Biology Laboratory, Heidelberg, Germany 4 Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, USA 5 Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands 6 ¨ Max-Delbruck-Centre for Molecular Medicine, Berlin, Germany 7 These authors contributed equally to this work. *Correspondence: linding@mshri.on.ca (R.L.), bork@embl.de (P.B.), myaffe@mit.edu (M.B.Y.), pawson@mshri.on.ca (T.P.) DOI 10.1016/j.cell.2007.05.052 SUMMARY by creating binding sites for protein interaction domains (for example, SH2 or BRCT) that selectively recognize
    • phosphoproteomics
    • in vivo phosphorylation sites
    • kinases are unknown
    • computational methods
    • overprediction
    • context
    • scaffolders Alberts, Molecular Biology of the Cell
    • interaction networks
    • NetworKIN
    • benchmarking
    • DNA damage response
    • experimental validation
    • take home message STRING and STITCH integrate information and predict interactions you can always go to the sources it’s useful!
    • Acknowledgements The STRING/STITCH team Lars Juhl Jensen Peer Bork Christian von Mering & group in Zurich NetworKIN Lars Juhl Jensen Rune Linding (and many other people)
    • Thank you for your attention
    • string.embl.de von Mering et al., NAR Database Issue 2007 stitch.embl.de Kuhn et al., NAR Database Issue 2008