STRING - Predicting novel metabolic pathways through the integration of diverse genome-scale data

STRING Predicting novel metabolic pathways through the integration of diverse genome-scale data Lars Juhl Jensen EMBL Heidelberg

Too much information – too little knowledge
Biology is now in the age of large-scale data collection
Explosive increase in data from genome sequencing, microarray expression studies, screening for protein interactions etc.
The data types are highly heterogeneous
Much data is not being deposited in standardized repositories
Most data sets are error-prone and suffer from systematic biases
STRING is a web resource that integrates many different types of information across 100+ species
Objective definition of metabolic pathways / functional modules
Prediction of additional pathway members / novel pathways
We do not intend STRING to be
a primary repository for experimental data
a curated database of complexes or pathways
a substitute for expert annotation

STRING provides a network of functional interactions between proteins Genomic neighborhood Species co-occurrence Gene fusions Database imports Exp. interaction data Microarray expression data Literature co-mentioning

Inferring functional modules from gene presence/absence patterns T rends in Microbiology Resting protuberances Protracted protuberance Cellulose © Trends Microbiol, 1999 Cell Cell wall Anchoring proteins Cellulosomes Cellulose The “Cellulosome”

Score calibration against a common reference
Many diverse types of evidence
The quality of each is judged by very different raw scores
These are all calibrated against the same reference set
Requirements for a reference
Must represent a compromise of the all types of evidence
Broad species coverage
Both a strength and a weakness
Scores for all evidence types are directly comparable
The type of interaction is currently not predicted

Multiple evidence types from several species

Objective definition of metabolic pathways Image: Molecular Biology of the Cell, 3 . rd edition Metabolism overview Defined manually: cutting metabolic maps into pathways Purine biosynthesis Histidine biosynthesis Defined objectively: standard clustering of genome-scale data

Getting more specific – generally speaking

Acknowledgments
The STRING team
Christian von Mering
Berend Snel
Martijn Huynen
Daniel Jaeggi
Steffen Schmidt
Mathilde Foglierini
Peer Bork
ArrayProspector web service
Julien Lagarde
Chris Workman
NetView visualization tool
Sean Hooper
Analysis of yeast cell cycle
Ulrik de Lichtenberg
Thomas Skøt
Anders Fausbøll
Søren Brunak
Web resources
string.embl.de
www.bork.embl.de/ArrayProspector
www.bork.embl.de/synonyms

Thank you!

STRING - Predicting novel metabolic pathways through the integration of diverse genome-scale data

by Lars Juhl Jensen

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STRING - Predicting novel metabolic pathways through the integration of diverse genome-scale data Presentation Transcript