Nature Biotechnology21, 1055 - 1062 (2003)
Published online: 17 August 2003; | doi:10.1038/nbt861
Discovery of uncharacterized cellular systems by genome-wide analysis
of functional linkages
Shailesh V Date1
& Edward M Marcotte1, 2
1
Center for Computational Biology and
Bioinformatics, Institute for Cellular and Molecular Biology, 1 University
Station A4800, Austin, Texas 78712-1064,
USA.
2
Department of Chemistry and Biochemistry, 1
University Station A4800, Austin, Texas
78712-1064, USA.
We introduce a general computational method, applicable on a
genome-wide scale, for the systematic discovery of uncharacterized cellular
systems. Quantitative analysis of the coinheritance of pairs of genes among
different organisms, calculated using phylogenetic profiles, allows the
prediction of thousands of functional linkages between the corresponding
proteins. A comparison of these functional linkages to known pathways reveals
that calculated linkages are comparable in accuracy to genome-wide yeast
two-hybrid screens or mass spectrometry interaction assays. In aggregate, these
linkages describe the structure of large-scale networks, with the resulting
yeast network composed of 3,875 linkages among 804 proteins, and the resulting
pathogenic Escherichia coli network composed of 2,043 linkages among 828
proteins. The search of such networks for groups of uncharacterized, linked
proteins led to the identification of 27 novel cellular systems from one
nonpathogenic and three pathogenic bacterial genomes.
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