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Nucleic Acids Research, 2003, Vol. 31, No. 24 7099-7109
© 2003 Oxford University Press

Article

Visualization and interpretation of protein networks in Mycobacterium tuberculosis based on hierarchical clustering of genome-wide functional linkage maps

Michael Strong1,2, Thomas G. Graeber1,2, Morgan Beeby2, Matteo Pellegrini3, Michael J. Thompson3, Todd O. Yeates2 and David Eisenberg*,1,2

1 Howard Hughes Medical Institute and 2 UCLA-DOE Institute of Genomics and Proteomics, Molecular Biology Institute, University of California at Los Angeles, Box 951570, Los Angeles, CA 90095-1570, USA and 3 Protein Pathways, 21111 Oxnard Street, Woodland Hills, CA 91367, USA

*To whom correspondence should be addressed. Tel: +1 310 206 3642; Fax: +1 310 206 3914; Email: david{at}mbi.ucla.edu

Genome-wide functional linkages among proteins in cellular complexes and metabolic pathways can be inferred from high throughput experimentation, such as DNA microarrays, or from bioinformatic analyses. Here we describe a method for the visualization and interpretation of genome-wide functional linkages inferred by the Rosetta Stone, Phylogenetic Profile, Operon and Conserved Gene Neighbor computational methods. This method involves the construction of a genome-wide functional linkage map, where each significant functional linkage between a pair of proteins is displayed on a two-dimensional scatter-plot, organized according to the order of genes along the chromosome. Subsequent hierarchical clustering of the map reveals clusters of genes with similar functional linkage profiles and facilitates the inference of protein function and the discovery of functionally linked gene clusters throughout the genome. We illustrate this method by applying it to the genome of the pathogenic bacterium Mycobacterium tuberculosis, assigning cellular functions to previously uncharacterized proteins involved in cell wall biosynthesis, signal transduction, chaperone activity, energy metabolism and polysaccharide biosynthesis.


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