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Using networks to derive function
 

Using networks to derive function

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Systems Biology Workshop, Technical University of Denmark, Lyngy, Denmark, May 14-15, 2009

Systems Biology Workshop, Technical University of Denmark, Lyngy, Denmark, May 14-15, 2009

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    Using networks to derive function Using networks to derive function Presentation Transcript

    • Using networks to derive function Lars Juhl Jensen
    • STRING
    • Jensen, Kuhn et al., Nucleic Acids Research , 2009
    • functional associations
    • Frishman et al., Modern Genome Annotation , 2009
    • common basis
    • 630 genomes
    • model organism databases
    • Ensembl
    • RefSeq
    • genomic context methods
    • gene fusion
    • Korbel et al., Nature Biotechnology , 2004
    • conserved neighborhood
    • operons
    • Korbel et al., Nature Biotechnology , 2004
    • bidirectional promoters
    • Korbel et al., Nature Biotechnology , 2004
    • phylogenetic profiles
    • Korbel et al., Nature Biotechnology , 2004
    • primary experimental data
    • protein interactions
    • yeast two-hybrid
    • affinity purification
    • fragment complementation
    • Jensen & Bork, Science , 2008
    • genetic interactions
    • Beyer et al., Nature Reviews Genetics , 2007
    • BIND Biomolecular Interaction Network Database
    • BioGRID General Repository for Interaction Datasets
    • DIP Database of Interacting Proteins
    • IntAct
    • MINT Molecular Interactions Database
    • HPRD Human Protein Reference Database
    • PDB Protein Data Bank
    • inferred associations
    • gene coexpression
    •  
    • GEO Gene Expression Omnibus
    • expression compendia
    • curated knowledge
    • complexes
    • MIPS Munich Information center for Protein Sequences
    • Gene Ontology
    • pathways
    • Letunic & Bork, Trends in Biochemical Sciences , 2008
    • KEGG Kyoto Encyclopedia of Genes and Genomes
    • MetaCyc
    • Reactome
    • PID NCI-Nature Pathway Interaction Database
    • literature mining
    • M EDLINE
    • SGD Saccharomyces Genome Database
    • The Interactive Fly
    • OMIM Online Mendelian Inheritance in Man
    • co-mentioning
    • statistical methods
    • NLP Natural Language Processing
      • Gene and protein names
      • Cue words for entity recognition
      • Verbs for relation extraction
      • [ nxgene The GAL4 gene ]
      • [ nxexpr T he expression of [ nxgene the cytochrome genes [ nxpg CYC1 and CYC7 ]]] is controlled by [ nxpg HAP1 ]
    •  
    • easy in theory …
    • … but not in practice
    • many data types
    • not comparable
    • variable quality
    • many sources
    • different file formats
    • different gene identifiers
    • partially redundant
    • spread over 630 genomes
    • quality scores
    • reproducibility
    • von Mering et al., Nucleic Acids Research , 2005
    • benchmarking
    • von Mering et al., Nucleic Acids Research , 2005
    • orthology
    • von Mering et al., Nucleic Acids Research , 2005
    • two modes
    • COG mode
    • von Mering et al., Nucleic Acids Research , 2005
    • protein mode
    • von Mering et al., Nucleic Acids Research , 2005
    • combine all evidence
    • Frishman et al., Modern Genome Annotation , 2009
    • Acknowledgments
      • Christian von Mering
      • Michael Kuhn
      • Manuel Stark
      • Samuel Chaffron
      • Philippe Julien
      • Tobias Doerks
      • Jan Korbel
      • Berend Snel
      • Martijn Huynen
      • Peer Bork