Interaction networks - Prediction, data integration and text mining

210
Lars Juhl Jensen Interaction networks Prediction, data integration and text mining

Transcript of Interaction networks - Prediction, data integration and text mining

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Lars Juhl Jensen

Interaction networksPrediction, data integration and text mining

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the cell cycle

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essential process

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grow and divide

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one cell

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two cells

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four phases

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G1 phase

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growth

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S phase

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DNA replication

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G2 phase

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growth

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M phase

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cell division

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regulation

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gene expression

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phosphorylation

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targeted degradation

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protein interactions

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exercise 1

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http://string-db.org

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Szklarczyk, Franceschini et al., Nucleic Acids Research, 2011

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association networks

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guilt by association

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STRING

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>1100 genomes

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genomic context

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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

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Korbel et al., Nature Biotechnology, 2004

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protein interactions

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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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gene coexpression

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curated knowledge

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Letunic & Bork, Trends in Biochemical Sciences, 2008

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>10 km

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text mining

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Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009

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co-mentioning

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NLPNatural Language Processing

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different sources

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Ensembl

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RefSeq

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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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GEOGene Expression Omnibus

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MIPSMunich Information center

for Protein Sequences

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Gene Ontology

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BioCyc

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KEGGKyoto Encyclopedia of Genes and Genomes

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PIDNCI-Nature Pathway Interaction Database

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Reactome

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different formats

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different names

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CDC2

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CDK1

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P06493

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not comparable

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variable quality

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confidence scores

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calibrate to gold standard

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von Mering et al., Nucleic Acids Research, 2005

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transfer by orthology

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von Mering et al., Nucleic Acids Research, 2005

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combine scores

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exercise 2

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changing parameters

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high confidence only

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experiments only

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evidence viewers

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cell cycle analysis

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gene expression

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cell cultures

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synchronization

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microarrays

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time courses

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Gauthier et al., Nucleic Acids Research, 2007

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cycling genes

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time of peak expression

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protein interactions

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temporal network

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de Lichtenberg, Jensen et al., Science, 2005

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just-in-time assembly

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de Lichtenberg, Jensen et al., Cell Cycle, 2007

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evolutionary flexibility

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orthologs and paralogs

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protein complexes

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exercise 3

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http://string-db.org

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network expansion

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what is known

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external data

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save network

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open in Cytoscape

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layout

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clustering

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project data onto network

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de Lichtenberg, Jensen et al., Science, 2005

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very flexible

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lose the STRING interface

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payload mechanism

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show external data

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nodes

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edges

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hosted on your server

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exercise 4

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http://cyclebase-string.jensenlab.org

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network expansion

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CDK–cyclin complexes

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chemical networks

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STITCH

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STRING + chemicals

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PubChem compounds

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>74,000 small molecules

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experimental data

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BindingDB

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ChEMBL

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PDSP KiPsycoactive Drug Screening Program

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PDBProtein Data Bank

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drug targets

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CTDComparative Toxicogenomics Database

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DrugBank

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GLIDAGPCR-Ligand Database

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Matador

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TTDTherapeutic Target Database

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metabolic pathways

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BioCyc

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KEGGKyoto Encyclopedia of Genes and Genomes

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Reactome

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text mining

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co-mentioning

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NLPNatural Language Processing

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same issues as for proteins

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only worse

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exercise 5

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http://stitch-db.org

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chemical network for TYMS

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Kuhn et al., Nucleic Acids Research, 2012

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network expansion

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interpretation

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disease networks

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human proteins

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>8,000 disease terms

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text mining

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co-mentioning

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exercise 6

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http://diseases.jensenlab.org

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TYMS disease associations

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inspect the evidence

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colorectal cancer network

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conclusions

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know your question

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know what is possible

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know the tools

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shameless self-promotion

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CONFIRMED SPEAKERS:Ivan DikicSteve JacksonJiri LukasAndre NussenzweigPhilippe BastiensTony PawsonForest WhiteEric VerdinTim HuntBrenda SchulmanMichael YaffeMatthias MannGerand HartSøren BrunakHenrik SembJuleen Zierath

CHAIRS:Jesper Velgaard OlsenChuna ChoudharyNiels MailandLars Juhl Jensen

REGISTRATION FEE, ACCOMMODATION AND LOCAL COSTS FOR ALL ATTENDEES ARE COVERED BY THE NOVO NORDISK FOUNDATION.

APPLICATION DEADLINE SEPTEMBER 14, 2012.

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larsjuhljensen

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thank you!