Data integration uncovers the metabolic bases of phenotypic variation in yeast

by Marianyela Sabina Petrizzelli, Dominique de Vienne, Thibault Nidelet, Camille No ûs, Christine Dillmann The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underl ying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species,Saccharomyces cerevisiae andS. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes. Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a highK was associated with high TCA fluxes, while a highJmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results. This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research