Open Access Highly Accessed Research article

Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network

Lan V Zhang1, Oliver D King1, Sharyl L Wong1, Debra S Goldberg1, Amy HY Tong2, Guillaume Lesage3, Brenda Andrews2, Howard Bussey3, Charles Boone2 and Frederick P Roth1*

Author affiliations

1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 USA

2 Banting and Best Department of Medical Research and Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5G 1L6, Canada

3 Department of Biology, McGill University, Montreal PQ H3A 1B1, Canada

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Citation and License

Journal of Biology 2005, 4:6  doi:10.1186/jbiol23

Published: 1 June 2005

Abstract

Background

Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction.

Results

To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products) and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' – classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions – the 'compensatory complexes' theme. Thematic maps – networks rendered in terms of such themes – can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes.

Conclusion

Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships.