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