Predicting phenotypic variation in yeast from individual genome sequences

被引:46
作者
Jelier, Rob [1 ]
Semple, Jennifer I. [1 ]
Garcia-Verdugo, Rosa [1 ]
Lehner, Ben [1 ,2 ]
机构
[1] Ctr Genom Regulat, European Mol Biol Lab, Syst Biol Res Unit, Barcelona, Spain
[2] Ctr Genom Regulat, ICREA, Barcelona, Spain
基金
欧洲研究理事会;
关键词
GENETIC INTERACTIONS; NETWORK; MUTATIONS;
D O I
10.1038/ng.1007
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
A central challenge in genetics is to predict phenotypic variation from individual genome sequences. Here we construct and evaluate phenotypic predictions for 19 strains of Saccharomyces cerevisiae. We use conservation-based methods to predict the impact of protein-coding variation within genes on protein function. We then rank strains using a prediction score that measures the total sum of function-altering changes in different sets of genes reported to influence over 100 phenotypes in genome-wide loss-of-function screens. We evaluate our predictions by comparing them with the observed growth rate and efficiency of 15 strains tested across 20 conditions in quantitative experiments. The median predictive performance, as measured by ROC AUC, was 0.76, and predictions were more accurate when the genes reported to influence a trait were highly connected in a functional gene network.
引用
收藏
页码:1270 / U141
页数:7
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