STRINGModeling of biological systems through

cross-species data integration

Lars Juhl JensenEMBL Heidelberg

Jensen et al., Drug Discovery Today: Targets, 2004

de Lichtenberg et al., Science, 2005

TOM

MRPLRibosome Related

MRPS

Vacuolar Acidification

Fatty Acid Biosynth.

Secondary RCC_Asy

RCC_Asy

RCCII

RCCIV

RCCVRCC_Asy

HAP Complex

Arg Biosynth.

PDH/KGD/GCV

Cell Wall & pH Reg.

DNA Repair

Glucose sensing and CH remodelling

APC

Fission/Fusion

rRNAProcessing

mRNAProcessing

TFIIICComplex

m-AAA Complex

TCA Cycle

Iron Homeostasis/Chaperone Activity

RCCI

rRNAProcessing

Leu/Val/IleBiosynth.

DNARepair

GARP Complex

Cytosolic Ribosome

TIM

RCC_Asy

Actin

tRNA Splicing

RCCIII

NUP

Replication/ DNA Repair

TOM

MRPLRibosome Related

MRPS

Vacuolar Acidification

Fatty Acid Biosynth.

Secondary RCC_Asy

RCC_Asy

RCCII

RCCIV

RCCVRCC_Asy

HAP Complex

Arg Biosynth.

PDH/KGD/GCV

Cell Wall & pH Reg.

DNA Repair

Glucose sensing and CH remodelling

APC

Fission/Fusion

rRNAProcessing

mRNAProcessing

TFIIICComplex

m-AAA Complex

TCA Cycle

Iron Homeostasis/Chaperone Activity

RCCI

rRNAProcessing

Leu/Val/IleBiosynth.

DNARepair

GARP Complex

Cytosolic Ribosome

TIM

RCC_Asy

Actin

tRNA Splicing

RCCIII

NUP

Replication/ DNA Repair

Protobacterialorthologs

TOM

MRPLRibosome Related

MRPS

Vacuolar Acidification

Fatty Acid Biosynth.

Secondary RCC_Asy

RCCII

RCCIVRCCV

RCC_Asy

HAP Complex

Arg Biosynth.

PDH/KGD/GCV

Cell Wall & pH Reg.

DNA Repair

Glucose sensing and CH remodelling

APC

Fission/Fusion

rRNAProcessing

mRNAProcessing

TFIIICComplex

m-AAA Complex

TCA Cycle

Iron Homeostasis/Chaperone Activity

RCCI

rRNAProcessing

Leu/Val/IleBiosynth.

DNARepair

GARP Complex

Cytosolic Ribosome

TIM

RCC_Asy

Actin

tRNA Splicing

RCCIII

NUP

Replication/ DNA Repair

Human diseaseorthologs

RCC_Asy

Genomic neighborhood

Species co-occurrence

Gene fusions

Database imports

Exp. interaction data

Microarray expression data

Literature co-mentioning

von Mering et al., Nucleic Acids Res., 2005

Restingprotuberances

Protractedprotuberance

Cellulose

© Trends Microbiol, 1999

CellCell wall

Anchoring proteins

Cellulosomes

Cellulose

The “Cellulosome”

Jensen et al., to appear in Nat. Rev. Genet., 2005

Networ-Kin™

Phospho-peptidedata (from MS)

Predict the kinase class(NetPhosK and Scansite)

Summary

• Quality control is crucial for large-scale data integration– The raw data sets from high-throughput experiments are dirty– Scoring, benchmarking, and filtering can greatly improve the

quality

• Data integration should be done across multiple species

• Automated literature mining methods are (finally) maturing– Restricted types of information can be extracted with high precision– Text mining methods can lead to novel discoveries

• Protein networks are more than just pretty pictures– Highly specific hypotheses can be made from high-quality

networks

Acknowledgments

• The STRING team– Christian von Mering

– Berend Snel

– Martijn Huynen

– Daniel Jaeggi

– Steffen Schmidt

– Sean Hooper

– Mathilde Foglierini

– Julien Lagarde

– Peer Bork

• Text mining project– Jasmin Saric

– Rossitza Ouzounova

– Isabel Rojas

• Networ-Kin– Rune Linding

– Tony Pawson

• Analysis of yeast mitochondria– Fabiana Perocchi

– Lars Steinmetz

• Analysis of yeast cell cycle– Ulrik de Lichtenberg

– Thomas Skøt

– Anders Fausbøll

– Søren Brunak

Thank you!