Discovery of uncharacterized cellular systems by genome-wide analysis of functional linkages.
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.
Date
Shailesh V
SV
Center for Computational Biology and Bioinformatics, Institute for Cellular and Molecular Biology, 1 University Station A4800, Austin, Texas 78712-1064, USA.
Marcotte
Edward M
EM
D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping / Q000379:methods*; D016000:Cluster Analysis; D004734:Energy Metabolism / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D016678:Genome; D010802:Phylogeny; D020543:Proteome / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein / Q000379:methods; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology
D001426:Bacterial Proteins; D020543:Proteome