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Protein interactions

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Lars Juhl Jensen
Lars Juhl Jensen
TechnologieBusiness
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Protein interactions Lars Juhl Jensen
what is an interaction?
physical interaction
functional association
fuzzy definitions
physical interactions
stable interactions
transient interactions
binary interactions
multimeric complexes
Jensen et al., Drug Discovery Today: TARGETS, 2004
spoke representation
Jensen et al., Drug Discovery Today: TARGETS, 2004
matrix representation
Jensen et al., Drug Discovery Today: TARGETS, 2004
interaction assays
yeast two-hybrid
fragment complementation
affinity purification
Jensen & Bork, Science, 2008
interaction databases
BioGRID General Repository for Interaction Datasets
DIP Database of Interacting Proteins
IntAct
MINT Molecular Interactions Database
Exercise 1 Go to http://thebiogrid.org Query for human TYMS Find the interaction partners Check their sources Think of possible problems
possibly many errors
only high-throughput
one assay
one study
functional associations
guilt by association
STRING
Franceschini et al., Nucleic Acids Research, 2013
Exercise 2 Go to http://string-db.org Query for human TYMS Show only highest confidence Show network in confidence view Show network in evidence view
genomic context
operons
Korbel et al., Nature Biotechnology, 2004
bidirectional promoters
Korbel et al., Nature Biotechnology, 2004
gene fusion
Korbel et al., Nature Biotechnology, 2004
phylogenetic profiles
Korbel et al., Nature Biotechnology, 2004
a real example
Cell Cellulosomes Cellulose
experimental data
physical interactions
Jensen & Bork, Science, 2008
genetic interactions
Beyer et al., Nature Reviews Genetics, 2007
gene coexpression
text mining
co-mentioning
curated knowledge
complexes
pathways
Letunic & Bork, Trends in Biochemical Sciences, 2008
many databases
different formats
different identifiers
variable quality
not comparable
not same species
hard work
(graduate students)
quality scores
von Mering et al., Nucleic Acids Research, 2005
calibrate vs. gold standard
von Mering et al., Nucleic Acids Research, 2005
homology-based transfer
orthologs vs. paralogs
Franceschini et al., Nucleic Acids Research, 2013
Exercise 3 Query STRING for human TYMS Show only experimental evidence Show up to 50 interaction partners Show also low-confidence links Redo exercise for mouse TYMS
related web resources
STITCH
STRING + 300k chemicals
drugs
metabolites
known drug targets
high-throughput screens
metabolic pathways
Exercise 4 Go to http://stitch-db.org Query for human TYMS What is the role of thymidylate? What is the role of dUMP? What is the role of Permetrexed?
general approach
suite of new resources
COMPARTMENTS
TISSUES
DISEASES
curated knowledge
experimental data
text mining
computational predictions
common identifiers
quality scores
visualization
compartments.jensenlab.org
tissues.jensenlab.org
thank you!

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