Technical University of Denmark, Lyngby, Denmark, December 14, 2004

1. STRING Prediction of a functional association network for the yeast mitochondrial system Lars Juhl Jensen EMBL Heidelberg

3. Part 1 Prediction of functional association between proteins Lars Juhl Jensen EMBL Heidelberg

4. What is STRING? Genomic neighborhood Species co-occurrence Gene fusions Database imports Exp. interaction data Microarray expression data Literature co-mentioning

6. 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”

7. Genomic context methods © Nature Biotechnology, 2004

9. Integrating physical interaction screens Make binary representation of complexes Yeast two-hybrid data sets are inherently binary Calculate score from number of (co-)occurrences Calculate score from non-shared partners Calibrate against KEGG maps Infer associations in other species Combine evidence from experiments

10. Mining microarray expression databases Re-normalize arrays by modern method to remove biases Build expression matrix Combine similar arrays by PCA Construct predictor by Gaussian kernel density estimation Calibrate against KEGG maps Infer associations in other species

12. Multiple evidence types from several species

13. Predicting and defining metabolic pathways and other functional modules 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

14. Part 2 The yeast mitochondrial system Lars Juhl Jensen EMBL Heidelberg

18. TOM MRPL Ribosome Related MRPS Vacuolar Acidification Fatty Acid Biosynth. Secondary RCC_Asy RCC_Asy RCCII RCCIV RCCV RCC_Asy HAP Complex Arg Biosynth. PDH/KGD/ GCV Cell Wall & pH Reg. DNA Repair Glucose sensing and CH remodelling APC Fission/ Fusion rRNA Processing mRNA Processing TFIIIC Complex m-AAA Complex TCA Cycle Iron Homeostasis/ Chaperone Activity RCCI rRNA Processing Leu/Val/Ile Biosynth. DNA Repair GARP Complex Cytosolic Ribosome TIM RCC_Asy Actin tRNA Splicing RCCIII NUP Replication/ DNA Repair

19. TOM MRPL Ribosome Related MRPS Vacuolar Acidification Fatty Acid Biosynth. Secondary RCC_Asy RCC_Asy RCCII RCCIV RCCV RCC_Asy HAP Complex Arg Biosynth. PDH/KGD/ GCV Cell Wall & pH Reg. DNA Repair Glucose sensing and CH remodelling APC Fission/ Fusion rRNA Processing mRNA Processing TFIIIC Complex m-AAA Complex TCA Cycle Iron Homeostasis/ Chaperone Activity RCCI rRNA Processing Leu/Val/Ile Biosynth. DNA Repair GARP Complex Cytosolic Ribosome TIM RCC_Asy Actin tRNA Splicing RCCIII NUP Replication/ DNA Repair Protobacterial orthologs

20. TOM MRPL Ribosome Related MRPS Vacuolar Acidification Fatty Acid Biosynth. Secondary RCC_Asy RCCII RCCIV RCCV RCC_Asy HAP Complex Arg Biosynth. PDH/KGD/ GCV Cell Wall & pH Reg. DNA Repair Glucose sensing and CH remodelling APC Fission/ Fusion rRNA Processing mRNA Processing TFIIIC Complex m-AAA Complex TCA Cycle Iron Homeostasis/ Chaperone Activity RCCI rRNA Processing Leu/Val/Ile Biosynth. DNA Repair GARP Complex Cytosolic Ribosome TIM RCC_Asy Actin tRNA Splicing RCCIII NUP Replication/ DNA Repair Human disease orthologs RCC_Asy

28. Thank you!