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Broad metabolic sensitivity profiling of a prototrophic yeast deletion collection VanderSluis, Benjamin; Hess, David C; Pesyna, Colin; Krumholz, Elias W; Syed, Tahin; Szappanos, Balázs; Nislow, Corey; Papp, Balázs; Troyanskaya, Olga G; Myers, Chad L; Caudy, Amy A
Abstract
Background: Genome-wide sensitivity screens in yeast have been immensely popular following the construction of a collection of deletion mutants of non-essential genes. However, the auxotrophic markers in this collection preclude experiments on minimal growth medium, one of the most informative metabolic environments. Here we present quantitative growth analysis for mutants in all 4,772 non-essential genes from our prototrophic deletion collection across a large set of metabolic conditions. Results The complete collection was grown in environments consisting of one of four possible carbon sources paired with one of seven nitrogen sources, for a total of 28 different well-defined metabolic environments. The relative contributions to mutants' fitness of each carbon and nitrogen source were determined using multivariate statistical methods. The mutant profiling recovered known and novel genes specific to the processing of nutrients and accurately predicted functional relationships, especially for metabolic functions. A benchmark of genome-scale metabolic network modeling is also given to demonstrate the level of agreement between current in silico predictions and hitherto unavailable experimental data. Conclusions These data address a fundamental deficiency in our understanding of the model eukaryote Saccharomyces cerevisiae and its response to the most basic of environments. While choice of carbon source has the greatest impact on cell growth, specific effects due to nitrogen source and interactions between the nutrients are frequent. We demonstrate utility in characterizing genes of unknown function and illustrate how these data can be integrated with other whole-genome screens to interpret similarities between seemingly diverse perturbation types.
Item Metadata
| Title |
Broad metabolic sensitivity profiling of a prototrophic yeast deletion collection
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| Creator | |
| Publisher |
BioMed Central
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| Date Issued |
2014-04-10
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| Description |
Background:
Genome-wide sensitivity screens in yeast have been immensely popular following the construction of a collection of deletion mutants of non-essential genes. However, the auxotrophic markers in this collection preclude experiments on minimal growth medium, one of the most informative metabolic environments. Here we present quantitative growth analysis for mutants in all 4,772 non-essential genes from our prototrophic deletion collection across a large set of metabolic conditions.
Results
The complete collection was grown in environments consisting of one of four possible carbon sources paired with one of seven nitrogen sources, for a total of 28 different well-defined metabolic environments. The relative contributions to mutants' fitness of each carbon and nitrogen source were determined using multivariate statistical methods. The mutant profiling recovered known and novel genes specific to the processing of nutrients and accurately predicted functional relationships, especially for metabolic functions. A benchmark of genome-scale metabolic network modeling is also given to demonstrate the level of agreement between current in silico predictions and hitherto unavailable experimental data.
Conclusions
These data address a fundamental deficiency in our understanding of the model eukaryote Saccharomyces cerevisiae and its response to the most basic of environments. While choice of carbon source has the greatest impact on cell growth, specific effects due to nitrogen source and interactions between the nutrients are frequent. We demonstrate utility in characterizing genes of unknown function and illustrate how these data can be integrated with other whole-genome screens to interpret similarities between seemingly diverse perturbation types.
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| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2015-12-18
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
Attribution 4.0 International (CC BY 4.0)
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| DOI |
10.14288/1.0221415
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| URI | |
| Affiliation | |
| Citation |
Genome Biology. 2014 Apr 10;15(4):R64
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| Publisher DOI |
10.1186/gb-2014-15-4-r64
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| Peer Review Status |
Reviewed
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| Scholarly Level |
Faculty
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| Copyright Holder |
VanderSluis et al.; licensee BioMed Central Ltd.
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| Rights URI | |
| Aggregated Source Repository |
DSpace
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Rights
Attribution 4.0 International (CC BY 4.0)