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Interaction networks - Prediction, data integration and text mining

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Lars Juhl Jensen
Lars Juhl Jensen
1 de 210
Interaction networks Prediction, data integration and text mining Lars Juhl Jensen
the cell cycle
essential process
grow and divide
one cell
two cells
four phases
G1 phase
growth
S phase
DNA replication
G2 phase
growth
M phase
cell division
regulation
gene expression
phosphorylation
targeted degradation
protein interactions
exercise 1
http://string-db.org
Szklarczyk, Franceschini et al., Nucleic Acids Research, 2011
association networks
guilt by association
STRING
>1100 genomes
genomic context
gene fusion
Korbel et al., Nature Biotechnology, 2004
conserved neighborhood
Korbel et al., Nature Biotechnology, 2004
phylogenetic profiles
Korbel et al., Nature Biotechnology, 2004
protein interactions
Jensen & Bork, Science, 2008
genetic interactions
Beyer et al., Nature Reviews Genetics, 2007
gene coexpression
curated knowledge
Letunic & Bork, Trends in Biochemical Sciences, 2008
>10 km
text mining
Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
co-mentioning
NLP Natural Language Processing
different sources
Ensembl
RefSeq
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
GEO Gene Expression Omnibus
MIPS Munich Information center for Protein Sequences
Gene Ontology
BioCyc
KEGG Kyoto Encyclopedia of Genes and Genomes
PID NCI-Nature Pathway Interaction Database
Reactome
different formats
different names
CDC2
CDK1
P06493
not comparable
variable quality
confidence scores
calibrate to gold standard
von Mering et al., Nucleic Acids Research, 2005
transfer by orthology
von Mering et al., Nucleic Acids Research, 2005
combine scores
exercise 2
changing parameters
high confidence only
experiments only
evidence viewers
cell cycle analysis
gene expression
cell cultures
synchronization
microarrays
time courses
Gauthier et al., Nucleic Acids Research, 2007
cycling genes
time of peak expression
protein interactions
temporal network
de Lichtenberg, Jensen et al., Science, 2005
just-in-time assembly
de Lichtenberg, Jensen et al., Cell Cycle, 2007
evolutionary flexibility
orthologs and paralogs
protein complexes
exercise 3
http://string-db.org
network expansion
what is known
external data
save network
open in Cytoscape
layout
clustering
project data onto network
de Lichtenberg, Jensen et al., Science, 2005
very flexible
lose the STRING interface
payload mechanism
show external data
nodes
edges
hosted on your server
exercise 4
http://cyclebase-string.jensenlab.org
network expansion
CDK–cyclin complexes
chemical networks
STITCH
STRING + chemicals
PubChem compounds
>74,000 small molecules
experimental data
BindingDB
ChEMBL
PDSP Ki Psycoactive Drug Screening Program
PDB Protein Data Bank
drug targets
CTD Comparative Toxicogenomics Database
DrugBank
GLIDA GPCR-Ligand Database
Matador
TTD Therapeutic Target Database
metabolic pathways
BioCyc
KEGG Kyoto Encyclopedia of Genes and Genomes
Reactome
text mining
co-mentioning
NLP Natural Language Processing
same issues as for proteins
only worse
exercise 5
http://stitch-db.org
chemical network for TYMS
Kuhn et al., Nucleic Acids Research, 2012
network expansion
interpretation
disease networks
human proteins
>8,000 disease terms
text mining
co-mentioning
exercise 6
http://diseases.jensenlab.org
TYMS disease associations
inspect the evidence
colorectal cancer network
conclusions
know your question
know what is possible
know the tools
shameless self-promotion
CONFIRMED SPEAKERS: Ivan Dikic Steve Jackson Jiri Lukas Andre Nussenzweig Philippe Bastiens Tony Pawson Forest White Eric Verdin Tim Hunt Brenda Schulman Michael Yaffe Matthias Mann Gerand Hart Søren Brunak Henrik Semb Juleen Zierath REGISTRATION FEE, ACCOMMODATION AND LOCAL COSTS FOR ALL ATTENDEES CHAIRS: ARE COVERED BY THE NOVO NORDISK Jesper Velgaard Olsen FOUNDATION. Chuna Choudhary Niels Mailand APPLICATION DEADLINE SEPTEMBER 14, Lars Juhl Jensen
larsjuhljensen
thank you!

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