• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Protein interactions
 

Protein interactions

on

  • 296 views

 

Statistics

Views

Total Views
296
Views on SlideShare
296
Embed Views
0

Actions

Likes
0
Downloads
4
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment
  • {}

Protein interactions Protein interactions Presentation Transcript

  • 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!