TY - JOUR
T1 - A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations
AU - Raamsdonk, Léonie M.
AU - Teusink, Bas
AU - Broadhurst, David Iain
AU - Zhang, Nianshu S.
AU - Hayes, Andrew
AU - Walsh, Michael C.
AU - Berden, Jan A.
AU - Brindle, Kevin M.
AU - Kell, Douglas B.
AU - Rowland, Jeremy John
N1 - Raamsdonk, L. M., Teusink, B., Broadhurst, D., Zhang, N. S., Hayes, A., Walsh, M. C., Berden, J. A., Brindle, K. M., Kell, D. B., Rowland, J. J., Westerhoff, H. V., van Dam, K., Oliver, S. G. (2001). A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nature Biotechnology, 19, (1), 45-50.
Sponsorship: EC contracts, within the frame of the EUROFAN program; grant from the UK's Biotechnology and Biological Sciences Research Council.
PY - 2001
Y1 - 2001
N2 - A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are 'silent,' that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing 'metabolic snapshots,' can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY—an abbreviation for functional analysis by co-responses in yeast.
AB - A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are 'silent,' that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing 'metabolic snapshots,' can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY—an abbreviation for functional analysis by co-responses in yeast.
U2 - 10.1038/83496
DO - 10.1038/83496
M3 - Article
SN - 1087-0156
VL - 19
SP - 45
EP - 50
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 1
ER -