Lars Juhl Jensen

Protein interactions

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

BioGRIDGeneral Repository for Interaction Datasets

DIPDatabase of Interacting Proteins

IntAct

MINTMolecular Interactions Database

Exercise 1Go 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 2Go 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 3Query 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 4Go 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!