Genome-scale metabolic model of the fission yeast Schizosaccharomyces pombe and the reconciliation of in silico/in vivo mutant growth

BMC Systems Biology

Sang Yup Lee²  Jay H Lee³  Tae Yong Kim¹  Seung Bum Sohn¹ 

[1] Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea;Department of Bio and Brain Engineering and Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea;Department of Chemical and Biomolecular Engineering (WCU Program), KAIST, Daejeon, Republic of Korea

关键词: Essentiality;    Single-gene mutant growth;    Genome-scale metabolic model;    Schizosaccharomyces pombe;   

Others  :  1144355
DOI  :  10.1186/1752-0509-6-49

 received in 2011-10-24, accepted in 2012-05-25,  发布年份 2012

【 摘 要 】

Background

Over the last decade, the genome-scale metabolic models have been playing increasingly important roles in elucidating metabolic characteristics of biological systems for a wide range of applications including, but not limited to, system-wide identification of drug targets and production of high value biochemical compounds. However, these genome-scale metabolic models must be able to first predict known in vivo phenotypes before it is applied towards these applications with high confidence. One benchmark for measuring the in silico capability in predicting in vivo phenotypes is the use of single-gene mutant libraries to measure the accuracy of knockout simulations in predicting mutant growth phenotypes.

Results

Here we employed a systematic and iterative process, designated as Reconciling In silico/in vivo mutaNt Growth (RING), to settle discrepancies between in silico prediction and in vivo observations to a newly reconstructed genome-scale metabolic model of the fission yeast, Schizosaccharomyces pombe, SpoMBEL1693. The predictive capabilities of the genome-scale metabolic model in predicting single-gene mutant growth phenotypes were measured against the single-gene mutant library of S. pombe. The use of RING resulted in improving the overall predictive capability of SpoMBEL1693 by 21.5%, from 61.2% to 82.7% (92.5% of the negative predictions matched the observed growth phenotype and 79.7% the positive predictions matched the observed growth phenotype).

Conclusion

This study presents validation and refinement of a newly reconstructed metabolic model of the yeast S. pombe, through improving the metabolic model’s predictive capabilities by reconciling the in silico predicted growth phenotypes of single-gene knockout mutants, with experimental in vivo growth data.

【 授权许可】

   
2012 Sohn et al.; licensee BioMed Central Ltd.

【 图 表 】

Fig. 13.

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