Netherlands Conference on Bioinformatics 2004, Hanzehogeschool, Groningen, Netherlands, October 7-8, 2004

1. STRING Prediction of functional relations, modules, and networks from heterogeneous genome-scale data Lars Juhl Jensen EMBL Heidelberg

3. STRING provides a modular protein network by integrating diverse types of evidence Genomic neighborhood Species co-occurrence Gene fusions Database imports Exp. interaction data Microarray expression data Literature co-mentioning

4. 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”

5. Genomic context methods © Nature Biotechnology, 2004

7. 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

8. 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

10. Multiple evidence types from several species

11. 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

16. Thank you!