STRING Modeling of biological systems through crossspecies data integration

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STRINGModeling of biological systems
throughcross-species data integration
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Lars Juhl Jensen
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promoter analysis
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Jensen et al., Bioinformatics, 2000
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genome visualization
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Pedersen et al., Journal of Molecular Biology,
2000
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protein function prediction
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STRING
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integrate diverse evidence
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functional interactions
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Bork et al., Current Opinion in Structural
Biology, 2005
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179 proteomes
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genomic context methods
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phylogenetic profiles
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Cell
Cellulosomes
Cellulose
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anti-correlated profiles
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analogous enzymes
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Morett et al., Nature Biotechnology, 2003
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gene neighborhood
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bidirectional promoters
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Korbel et al., Nature Biotechnology, 2004
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gene fusion
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evolution
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statistics
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(the original sin)
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scoring and benchmarking
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raw quality scores
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gene neighborhood
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sum of intergenic distances
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many types of evidence
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not directly comparable
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calibrate vs. gold standard
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curated knowledge
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KEGG Kyoto Encyclopedia of Genes and Genomes
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STKE Signal Transduction Knowledge Environment
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Reactome
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MIPS Munich Information center for Protein
Sequences
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primary experimental data
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Jensen et al., Drug Discovery Today Targets, 2004
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microarray expression data
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GEO Gene Expression Omnibus
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physical protein interactions
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BIND Biomolecular Interaction Network Database
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MINT Molecular Interactions Database
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GRID General Repository for Interaction Datasets
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DIP Database of Interacting Proteins
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HPRD Human Protein Reference Database
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von Mering et al., Nucleic Acids Research, 2005
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literature mining
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MEDLINE
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SGD Saccharomyces Genome Database
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The Interactive Fly
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OMIM Online Mendelian Inheritance in Man
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co-mentioning
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different gene names
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curated synonyms lists
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NLP Natural Language Processing
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• Gene and protein names
• Cue words for entity recognition
• Verbs for relation extraction
• nxgene The GAL4 gene
• nxexpr The expression of nxgene the
  cytochrome genes nxpg CYC1 and
  CYC7is controlled bynxpg HAP1

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Jensen et al., Nature Reviews Genetics, 2006
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combine all evidence
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naïve Bayesian scheme
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spread over many species
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transfer based orthology
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Target species
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Source species
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defining functional modules
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qualitative modeling
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the mitochondrial system
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RCCs
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predicting mode of action
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Jensen et al., Drug Discovery Today Targets, 2004
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Jensen et al., Drug Discovery Today Targets, 2004
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Acknowledgments

• The STRING team (EMBL)
• Christian von Mering
• Berend Snel
• Martijn Huynen
• Sean Hooper
• Mathilde Foglierini
• Julien Lagarde
• Peer Bork
• Literature mining project(EML Research)
• Jasmin Saric
• Rossitza Ouzounova
• Isabel Rojas

• New genomic context methods (EMBL)
• Jan Korbel
• Peer Bork
• Modeling of yeast mitochondria (EMBL)
• Fabiana Perocchi
• Lars Steinmetz
• Inspiration for presentation
• Dick Clarence Hardt
• Anders Gorm Pedersen

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Thank you!