title: Metabolomics-based systematic prediction of yeast lifespan and its application for semi-rational screening of ageing-related mutants.
abstract: Metabolomics - the comprehensive analysis of metabolites - was recently used to classify yeast mutants with no overt phenotype using raw data as metabolic fingerprints or footprints. In this study, we demonstrate the estimation of a complicated phenotype, longevity, and semi-rational screening for relevant mutants using metabolic profiles as strain-specific fingerprints. The fingerprints used in our experiments are profiled data consisting of individually identified and quantified metabolites rather than raw spectrum data. We chose yeast replicative lifespan as a model phenotype. Several yeast mutants that affect lifespan were selected for analysis, and they were subjected to metabolic profiling using mass spectrometry. Fingerprinting based on the profiles revealed a correlation between lifespan and metabolic profile. Amino acids and nucleotide derivatives were the main contributors to this correlation. Furthermore, we established a multivariate model to predict lifespan from a metabolic profile. The model facilitated the identification of putative longevity mutants. This work represents a novel approach to evaluate and screen complicated and quantitative phenotype by means of metabolomics.
authors.affiliation: Department of Biotechnology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yoshida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tamura
authors.forename: Chika
authors.initials: C
authors.lastname: Takaoka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Harada
authors.forename: Akio
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Mukai
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
mesh_terms: D005800:Genes, Fungal / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors