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Lars Juhl Jensen Data integration and functional association networks

Data integration and functional association networks

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Exploring Modular Protein Architecture, European Molecular Biology Laboratory, Heidelberg, Germany, December 3-5, 2008

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Page 1: Data integration and functional association networks

Lars Juhl Jensen

Data integration and functional association

networks

Page 2: Data integration and functional association networks

Lars Juhl Jensen

Data integration and functional association

networks

Page 3: Data integration and functional association networks

if this is your plan

Page 4: Data integration and functional association networks
Page 5: Data integration and functional association networks
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STRING

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Jensen, Kuhn et al., Nucleic Acids Research, 2009

Page 8: Data integration and functional association networks

data integration

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functional associations

Page 10: Data integration and functional association networks

Frishman et al., Modern Genome Annotation, 2009

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the 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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Korbel et al., Nature Biotechnology, 2004

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phylogenetic profiles

Page 22: Data integration and functional association networks

Korbel et al., Nature Biotechnology, 2004

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primary experimental data

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gene coexpression

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GEOGene Expression Omnibus

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protein interactions

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Jensen & Bork, Science, 2008

Page 29: Data integration and functional association networks

BINDBiomolecular Interaction Network Database

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BioGRIDGeneral Repository for Interaction Datasets

Page 31: Data integration and functional association networks

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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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

Page 42: Data integration and functional association networks

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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thesaurus

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co-mentioning

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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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too easy …

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… to be true

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many data types

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not comparable

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different error rates

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many sources

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different file formats

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different gene identifiers

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redundancy

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spread over 630 genomes

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raw quality scores

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reproducibility

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von Mering et al., Nucleic Acids Research, 2005

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intergenic distances

Page 70: Data integration and functional association networks

Korbel et al., Nature Biotechnology, 2004

Page 71: Data integration and functional association networks

benchmarking

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calibrate vs. gold standard

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von Mering et al., Nucleic Acids Research, 2005

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raw quality scores

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probabilistic scores

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transfer by 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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visualize

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Frishman et al., Modern Genome Annotation, 2009

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related resources

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STITCH

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protein–chemical network

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Reflect

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eggNOG

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orthologous groups

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NetworKIN

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Linding, Jensen, Ostheimer et al., Cell, 2007

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Acknowledgments

NetworKIN.info– Rune Linding

– Gerard Ostheimer

– Francesca Diella

– Karen Colwill

– Jing Jin

– Pavel Metalnikov

– Vivian Nguyen

– Adrian Pasculescu

– Jin Gyoon Park

– Leona D. Samson

– Rob Russell

– Peer Bork

– Michael Yaffe

– Tony Pawson

STRING.embl.de– Michael Kuhn– Manuel Stark– Samuel Chaffron– Chris Creevey– Jean Muller– Tobias Doerks– Philippe Julien– Alexander Roth– Milan Simonovic– Peer Bork– Christian von Mering

STITCH.embl.de– Michael Kuhn– Christian von Mering– Monica Campillos– Peer Bork

eggNOG.embl.de– Philippe Julien– Michael Kuhn– Christian von Mering– Jean Muller– Tobias Doerks– Peer Bork

Reflect.ws– Sean O’Donoghue– Evangelos Pafilis– Heiko Horn– Michael Kuhn– Peer Bork– Reinhardt Schneider